SUPPLIER and WLA PHARMASE are the parties to this Agreement. This constitutes the Quality Technical Agreement (hereinafter referred to as QTA) covering contract Distribution activities in accordance with the principles and guidelines for Good Distribution Practices (GDP)

Since the QTA covers also Clinical Trials drugs, current Good Clinical Practices applies as well.

1. SCOPE

This QTA defines the scopes and the individual responsibilities of WLA PHARMASE (the contract giver) and SUPPLIER and in particular defines the roles of responsible persons of the Parties.

Key contact persons are listed in Attachment 2 of this QTA.

This QTA takes the form of a detailed checklist of the main activities associated with Storage and Distribution of Products for Investigational Medicinal Products (IMPs). Responsibility for each activity is assigned to either WLA PHARMASE or SUPPLIER by marking the relevant box with an “X”.

Each party shall perform its respective obligations under this QTA in accordance with all applicable laws, including, without limitations, cGDP
When WLA PHARMASE IMPs are nominated along the document, it shall mean the Products as listed in Attachment 3 of this QTA.

2. ORDER OF PRECEDENCE

This QTA is attached to the agreement referenced in the heading of this QTA (the Master Agreement between WLA PHARMASE and SUPPLIER) and constitutes an integral part of it. As regards technical and quality aspects of the Storage and Distribution of the Products, the Master Agreement refers to this QTA. The Parties acknowledge and agree that in the event of conflict, inconsistency or discrepancy between the Master Agreement and any terms and conditions contained in this QTA, the order of precedence as set forth in the Main Agreement applies. However, with regard solely to technical and quality related aspects, this QTA shall prevail.

3. TERM

This QTA shall commence on execution thereof by the Parties and shall expire or terminate upon the expiration or termination of the Master Agreement.

4. AMENDMENTS

Any amendment to this QTA shall be made in writing or, if limited to its attachments, by the following procedure:

If an Attachment has to be amended, it shall be replaced by a new version (with a new version number) and shall be duly executed by each Party’s quality responsible person.

The new version of an Attachment amended by both Parties shall enter into force on the effective date set forth in the new version of the respective Attachment.

SUPPLIER shall then update Attachment 1 (Amendment History) accordingly.

However, Attachment 2 (Key contact persons) of this QTA may be unilaterally modified by the Party concerned and shall enter into force upon receipt of the notification by the other Party. The other Party shall confirm the receipt of the new version of the respective Attachment by signature; insert the date of receipt of the amended version of the Attachment.

SUPPLIER shall then update Attachment 1 (Amendment History) accordingly.

Any unilateral amendment of Attachment 5 (Record of permitted subcontractors) is subject to section 3 of this document (Sub-contracting).

If applicable, SUPPLIER shall provide WLA PHARMASE with the current list of sub-contractors every January and July of a calendar year and moreover, WLA PHARMASE may request the (updated) list in Attachment 5 at any time and shall receive such list within 24 hours from its request.

5. REPORTS

Any reports or other information due under this QTA shall be sent to the Key contact persons of the other Party.

6. REFERENCE

The document representing the QTA between SUPPLIER and WLA PHARMASE has been written in accordance with current regulation in terms oGDP.

2. DEFINITIONS

Unless specifically defined in this QTA, all capitalized terms shall have the meaning as set forth below.

“Affiliate” means, with respect to each Party, any company (i) 50% or more of whose outstanding securities or assets are owned or controlled, directly or indirectly, by said Party, (ii) which owns or controls, directly or indirectly, 50% or more of the outstanding securities or assets of said Party, or (iii) any company owned or controlled, directly or indirectly, to the extent of 50% or more of the outstanding securities or assets, by any of the companies

Described in (i) or (ii) above or (iv) any company that is under the common control of any of said companies according to (i), (ii) or (iii).

“Business Day” shall mean every day of a week with the exception of Saturday or Sunday or any public holiday in countries of the Parties concerned.

“CAPA” shall mean the process of defining a Corrective Action/Preventive Action plan; it is required for audit findings, deviations, non-conformance, complaints, etc.

“Clinical Trial (CT) Drugs” shall mean IMPs (investigational medicinal products) and non-IMPs or materials for use in clinical trials

“Current Good Distribution Practices (cGDP)” shall mean the part of quality assurance that ensures that the quality of a pharmaceutical product is maintained by means of adequate control of the numerous activities which occur throughout the distribution process.

“Current Good Manufacturing Practices (cGMP)” shall mean the part of quality assurance which ensures that pharmaceutical products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.

“Current Good Clinical Practices (cGCP)” shall mean the part of quality which defines standards on how clinical trials should be conducted, the roles and the responsibilities of clinical trial sponsor, clinical research investigators and monitors

“Finished Product” shall mean all sales goods and/or samples in their final labelled and packaged form suitable for distribution to the market, foreseen for Storage and Distribution.

“First Expired/First out (FEFO)” shall mean Distribution procedure that ensures that the stock with the earliest expiry date is distributed and/or used before an identical stock item

With a later expiry date is distributed and/or used; earliest expired/first out (EEFO) has a similar meaning.

“Logistic Complaint” shall mean any written, or electronic or by other means communicated expression of issue regarding Products generated as part of the logistic process; this includes, but not limited to, damages from transportation, incorrect quantities, exposure to temperature different from expected.

“Parties” shall mean SUPPLIER and/or WLA PHARMASE.

“Product Complaint” shall mean any written, or electronic or by other means communicated expression of dissatisfaction regarding Products including, but not limited to, actual or suspected product tampering, contamination, mislabelling, wrong ingredients, or adverse events.

“Product recall” shall mean the process for withdrawing or removing a pharmaceutical product from the pharmaceutical Distribution chain because of defects in the product or complaints of serious adverse reactions to the product.

“Quarantine” shall mean the status of pharmaceutical products isolated physically or by other effective means while a decision is awaited on their release, rejection or reprocessing.

“Responsible Person” shall mean a person who fulfills all qualifications and conditions provided for by applicable law; in the European Union, this shall include, where applicable, a

“qualified person” within the meaning of Article 48 of Directive 2001/83/EC of 6 November 2001 on the Community code relating to medicinal products for human use, in non-EU countries it shall be understood as referring to a person with equivalent qualification and responsibilities.

“Retention Sample” shall mean the sample of a fully packaged unit from a batch of Finished Product. The Retention Sample includes e.g. presentation, packaging, labelling, patient information leaflet, Batch number, expiry date.

“Secondary Packaging Material” shall mean any packaging material, which is not and may not be in direct contact with Bulk Drug Product.

“Storage” shall mean the storing of pharmaceutical Products up to the point of use.

“Transportation” shall mean the delivery and movement of pharmaceutical products from the premises of the manufacturer of such products, or another central point, to the end user thereof, or to an intermediate point by means of various transport methods, including all intermediate storage and loading/unloading activities.

3. SUB-CONTRACTING

SUPPLIER shall not be entitled to sub-contract or assign its obligations under this QTA, whether in whole or in part, to any third party, including but not limited to its Affiliates, without the prior evaluation of the arrangements by WLA PHARMASE and the prior written consent of WLA PHARMASE.

SUPPLIER may engage sub-contractors in conformity with its own quality system and WLA PHARMASE’s consent shall be deemed given under the following conditions:

(i) The respective sub-contractor fits into the respective qualitysystem of SUPPLIER, which shall be checked actively by SUPPLIER according to its quality system (e.g. via basic check and regular audits),

(ii) SUPPLIER gives WLA PHARMASE reasonable advance written notice, in no event less than two (2) weeks, of its intention to sub-contract,

(iii) With the notice, provides the relevant information, including its quality guidelines, for WLA PHARMASEto evaluate the arrangements, and

(iv) WLA PHARMASE does not object in writing within the reasonable notice period.

WLA PHARMASE has the right to object to a specific sub-contractor and request its deletion from the list of sub-contractors at any time for cause, such as any damage, or risk of damage, to WLA PHARMASE resulting from the respective sub-contractor or any bad performance.

Where in accordance with the terms of this QTA, SUPPLIER sub-contracts some or all of its obligations under this QTA, SUPPLIER respectively shall, subject to the terms of the Main agreement, be responsible for all the acts and omissions of any such sub-contractor(s) as if the acts and/or omissions had been carried out by it.

A list of agreed sub-contractors is attached to this QTA as Attachment 5 and will be updated by SUPPLIER pursuant to section 1.4 above.

4. AUDITING

Upon reasonable prior notice as is appropriate under the circumstances, SUPPLIER shall permit WLA PHARMASE and/or its designated representative(s) and/or a competent regulatory authority to audit (e.g. regular, operational, follow-up, for cause audits) SUPPLIER plants or its sub-contractors’ facilities, equipment, QA system and the documentation which are related to the performance of its obligations under this QTA at any time during normal working hours.

In case of emergencies (such as for example but not limited to anticipated or potential breach of contract) it will be reasonable for such audits to be performed exceptionally upon very short prior notice (which may mean a prior oral warning of a few hours or less, as circumstances require).

SUPPLIER shall promptly, however no later than one (1) month after the receipt of any audit report, provide a written response to WLA PHARMASE with the corrective and preventive actions. SUPPLIER shall implement appropriate corrective and preventive actions within the timelines agreed upon by the Parties.

WLA PHARMASE will review the CAPA plan and provide comments if necessary.

Once CAPA plan is agreed by both Parties, WLA PHARMASE will expect that it is completed in the terms and timelines as it is written. In case for any reason SUPPLIER cannot complete the CAPA plan, the reason and the new timeline will be communicated to WLA PHARMASE before due date is overdue.

For CAPA plan which takes more than 6 months, every 6 months a feedback from SUPPLIER to WLA PHARMASE on the progress of the CAPA plan (follow up) is desirable. Nevertheless CAPAs has to be closed within the duration of the present agreement.

SUPPLIER shall notify WLA PHARMASE without undue delay, but no later than three (3) Business days of any authority contact, including any audits/inspections or actions by the regulatory authority or other customers which could potentially impact on the SUPPLIER license or on Products.

Any information shared during an audit shall be treated as confidential and for the use within the Parties involved only.

5. TABLE OF RESPONSIBILITIES

7.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.1	8. General
5.1.1	SUPPLIER will perform storage activities for shipments provided by WLA PHARMASE in accordance with the main contract and this QTA. He will also fully comply with GDP requirements, with all applicable legislation and instructions from Italian Authorities.	—	X
5.1.2	SUPPLIER will perform transportation activities for shipments provided by WLA PHARMASE in accordance with the main contract and this QTA. He will also fully comply with GDP requirements, with all applicable legislation and instructions from Italian Authorities.	—	X
5.1.3	SUPPLIER also ensures compliance with all applicable laws and regulations regarding environmental, health and safety aspects for both his organization and his sub-contractors’ organization.	—	X
5.1.4	The system for managing quality shall encompass the organizational structure, procedures, processes and resources, as well as activities necessary to ensure confidence that the Product maintains its quality and integrity and remains within the legal supply chain during all Storage and Distribution Activities.	—	X
5.1.5	The quality system shall be fully documented and its effectiveness monitored. All quality system-related activities shall be defined and documented. A quality manual or equivalent documentation approach shall be established.	—	X
5.1.6	A responsible person shall be appointed by the management, who shall have clearly specified authority and responsibility for ensuring that a quality system is implemented and maintained.	—	X
5.1.7	The management of supplier shall ensure that all parts of the quality system are adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities.	—	X
5.1.8	The size, structure and complexity of SUPPLIER and SUPPLIER ‘s activities shall be taken into consideration when developing or modifying the quality system. A change control system shall be in place. This system shall incorporate quality risk management principles, and be proportionate and effective.	—	X

9

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.1.9	The quality system at SUPPLIER and SUPPLIER’s organization shall ensure that: ü Products are received, held, arranged and transported in a way that is compliant with the requirements of GDP (SUPPLIER) ü Management responsibilities are clearly specified; ü Products are delivered to the right recipients within a satisfactory time period; ü Records are made contemporaneously; ü Deviations from established procedures are documented and investigated; ü Appropriate corrective and preventive actions (commonly known as CAPA) are taken to correct deviations and prevent them in line with the principles of quality risk management.	—	X
5.1.10	The above quality assurance system shall explicitly cover sub-contractors, i.e. a system to qualify the sub-contractor(s) in accordance with the established quality procedures and in compliance with all applicable law. This means that SUPPLIER will perform audits on his sub-contractor(s) on periodic basis according to his audit plan against common and applicable standards.	—	X
5.1.11	In case of non conformities verified during the audit on sub-contractors, SUPPLIER have to send info to WLA PHARMASE within one business day	—	X
5.1.12	The SUPPLIER and his sub-contractors shall be permanently in the possession of all necessary permits and authorizations required by the Italian applicable law for Storage Activities and Transportation Activities for Products. The SUPPLIER shall provide WLA PHARMASE copies of the respective permits, approvals and authorizations upon request.	—	X
5.1.13	Provide to SUPPLIER specific instructions in case of specific service.	X	—
5.1.14	Provide to SUPPLIER the following information are mandatory for routine activities: Product requiring cold chain conditions Managing instruction Operative instruction In case of any change to the list, WLA PHARMASE has to immediately update it and provide it to SUPPLIER.	X	—
5.1.15	In particular circumstances WLA PHARMASE has to provide to SUPPLIER also information regarding Product description, quantities and Storage conditions and any other necessary information, in order SUPPLIER can fulfil all activities covered by the present agreement	X	—

10

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.2	11. PERSONNEL
5.2.1	Appoint a Responsible Person if applicable according to local law for each warehouse (should be a pharmacist), in possession of qualification and all conditions provided for by the applicable law. The Responsible Person shall have appropriate competence, experience and knowledge. The Responsible Person shall also maintain his/her competence in GDP through regular training. The SUPPLIER shall provide WLA PHARMASE evidence that Responsible Person for each warehouse is in possession of qualification and all conditions provided for by the applicable law.	—	X
5.2.2	The Responsible Person shall carry out his/her duties in such a way as to ensure that GDP compliance can be proved. Core responsibilities of Responsible Person are (but not limited) as follows: ü Quality management system is implemented and maintained; ü All activities performed are authorized; ü Records are accurate, complete and correct; ü Records of delegation duties are maintained; ü Training program (initial and on-going) are defined and completed; ü complaints (if any) are managed properly and in accordance with WLA PHARMASE procedures; ü Suppliers and customer are qualified/approved; ü Contract including GDP relevance with third parties are available, regularly reviewed and approved; ü Self-inspection program is in place and is followed and documented;	—	X
5.2.3	The Responsible Person shall fulfil his/her responsibilities personally and shall be continuously contactable. The written job description of the Responsible Person shall define his/her authority to take decisions with regard to his/her responsibilities. SUPPLIER shall assure in practice the Responsible Person has the defined authority, resources and responsibility needed to fulfil his/her duties. A back up should formally be appointed to assure a Responsible Person is always available; back up function for RP role are included in Attachment 2. The SUPPLIER shall provide WLA PHARMASE evidence that the written job description of the Responsible Person shall define his/her authority to take decisions with regard to his/her responsibilities	—	X
5.2.4	Ensure that there is an adequate number of competent qualified personnel involved in all the tasks for which the SUPPLIER is responsible who have the education, training and experience or any combination thereof to perform the assigned function with particular training on IMPs management. The number will depend on the volume of activities performed. This expectation is extended also to personnel engaged in Transportation. In both cases all training shall be documented.	—	X
5.2.5	Appoint a Quality Manager in possession of qualification and all conditions provided for by the applicable law referred to GDP activities. The Quality Manager shall have appropriate competence, experience and knowledge. The Quality Manager shall also maintain his/her competence in GDP through regular training.	—	X

12

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.2.6	All personnel involved both in the Warehousing Activities and in Transportation shall be trained on the requirements of GDP. They shall have the appropriate competence and experience prior to commencing their tasks. This is valid also in case of change in role within the organization. Personnel shall receive initial and continuing training relevant to their role, based on written procedures and in accordance with a written training program. Training shall include aspects of product identification and avoidance of falsified medicines entering the supply chain.	—	X
5.2.7	An organization chart clearly indicating name, role and reporting lines and written Job Description for Responsible Person and key functions in SUPPLIER’s organization should be available. SUPPLIER has to ensure that individual responsibilities are clearly understood by the staff and recorded.	—	X
5.2.8	Significant changes in organization must be notified to WLA PHARMASE in advance in order to enable WLA PHARMASE to assess the possible impact on Products.	—	X
5.2.9	In case of products which require particular handling, personnel should receive a specific training. Examples of such products are: hazardous products, radioactive materials, products presenting special risks of abuse (including narcotic and psychotropic substances), and temperature-sensitive products.	—	X
5.2.10	All training delivered should be documented and when applicable effectiveness should be demonstrated before people can operate alone. On periodic basis training effectiveness should be assessed and documented. Training records should be kept and provided to WLA PHARMASE on request.	—	X
5.2.11	An appropriate procedure should be in place to cover health, personnel hygiene and gowning practices; the procedure should prohibit the entrance of food, drink, smoking materials and medication for personal use in the working area.	—	X

13

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.3		14. TRANSIT-POINTS
*ENVIRONMENTAL CONDITIONS*
5.3.1	SUPPLIER must have suitable and adequate premises, installations and equipment, so as to ensure proper storage of Products. In particular, the premises shall be clean, dry and maintained within acceptable temperature limits.		—	X
5.3.2	SUPPLIER must have suitable and adequate premises, installations and equipment, so as to ensure proper distribution of Products. In particular, the premises shall be clean, dry and maintained within acceptable temperature limits.		—	X
5.3.3	An initial temperature mapping exercise shall be carried out on the storage area, including cold rooms, before use, under representative conditions. Temperature monitoring equipment shall be located according to the results of the mapping exercise, ensuring that monitoring devices are positioned in the areas that experience the extremes of fluctuations. The initial mapping study has to consider the two alternate seasons as they represent the worst case. As conventional rule winter period is considered from mid-December to mid-February, while summer period is from end June to end August.		—	X
5.3.4	The mapping exercise shall be repeated according to the results of a risk assessment exercise or whenever significant modifications are made to the facility or the temperature controlling equipment.		—	X
5.3.5	Environmental conditions which may affect product quality during storage should be defined and monitored 24 h/7 days. An alarm system is in place to detect any significant deviations from pre-defined values. Ensure alarm level is set appropriately (considering the instrument tolerance) and regularly verified to confirm proper functionality.		—	X
5.3.6	Monitored temperature data shall be periodically (at least every week) reviewed by Responsible Person if applicable (SUPPLIER) and/or QA department (SUPPLIER): any discrepancy found has to be communicated without any delay to Sponsor/WLA PHARMASE, as defined in the Work Instructions, and analyzed. Those data have to be made available for inspection by the regulatory or other oversight body or for audits by WLA PHARMASE.		—	X
5.3.7	All Temperature raw data shall be kept in a suitable archive for a minimum 7 years.		—	X
5.3.8	Design premises (or adapt) in a way to ensure required storage condition are maintained; this includes also enough space and lighting, to enable all operations to be carried out accurately and safely. Rest, wash and refreshment rooms should be separate from storage area.		—	X
5.3.9	Receiving and dispatch should be designed in a way to protect goods from adverse conditions. There shall be adequate separation between the receipt and dispatch and storage areas. Receiving area should be broad enough to contain products waiting for examination. Procedures shall be in place to maintain control of inbound/ outbound goods.		—	X
5.3.10	General access to warehouses shall be restricted to authorized personnel and controlled. At this purpose SUPPLIER shall adopt a monitored intruder alarm system and an appropriate access control system. Visitors shall always be accompanied.		—	X

15.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

SPECIFIC STORAGE LOCATION (RETURNS, DAMAGED SHIPMENTS, ecc)
5.3.11	Access to specific areas within warehouses shall be limited only to authorized personnel; an access control system shall be in place for those restricted locations.	—	X
5.3.12	Products which require specific measure (e. g. radioactive or explosive or inflammable products) should be stored in one or more dedicated and separated areas with all necessary safety and security measures.	—	X
5.3.13	IMPs has to be stored in a dedicated restricted and separate area. Only authorized personnel can access to CT Drugs.	—	X
5.3.14	Narcotics and psychotropic substances shall be stored in a separate and access controlled area according to Italian law requirements. All special authorization for such products have to be obtained and maintained updated.	—	X
5.3.15	Returns products shall be positioned in a dedicated and access controlled area waiting for the evaluation.	—	X
5.3.16	Products pending a decision as to their disposition (in quarantined or waiting status) shall be segregated either physically or through an equivalent electronic system. Same approach shall be applied for product received from a foreign country located outside the European Community.	—	X
5.3.17	Products removed from saleable stock for any reasons and intended for disposal (expired, damaged, rejected, ecc) shall be physically segregated and stored in a dedicated area away from all other Products. This area shall be access controlled and clearly identified; electronic system shall be aligned with physical location. This includes, for example, any falsified product or suspected of falsification, returned products which have not passed the evaluation step.	—	X

16

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

*SAFETY MEASURES*
5.3.18	Warehouse should be designed in such a way all possible safety risks are minimized for both people and goods. For example fire protection, material of construction, segregation of dangerous goods; emergency routes are some of the possible measures to mitigate risk.	—	X
17. CLEANING AND PEST CONTROL
5.3.19	Prevent Products contamination from any source such as but not limited to insect, rodent, or any pest, litter and dust.	—	X
5.3.20	Maintain Storage/transit point facilities in a clean and well organised manner. Define cleaning program and cleaning instructions, schedule, and document and verify cleaning activities.	—	X
5.3.21	If used, cleaning equipment and or cleaning agents should not be source of contamination for Products; cleaning agents are formally approved by the management. No fumigation agents are allowed.	—	X
5.3.22	Implement a comprehensive pest control program that includes but is not limited to details of the bait locations and insects, the chemicals used and the frequency of inspection for pest activity. Record details of inspections performed and actions taken	—	X

18

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.4

EQUIPMENT & SYSTEM

5.4.1	Ensure equipment and computer systems with direct/indirect impact on goods quality (ex: stock management, temperature monitoring/control, etc.) are secure and validated before use, in compliance with Annex 11 and 15 of EU GMP Guide. Qualification/Validation should demonstrate that the equipment/system is able to achieve the desired results in a consistent, accurate and reproducible manner. Qualification/Validation reports should be prepared summarizing the results obtained and commenting on any observed deviations. Deviations from established procedures shall be documented and further actions decided to correct deviations and avoid their reoccurrence (corrective and preventive actions). Evidence of satisfactory validation and acceptance of a process or piece of equipment shall be produced and approved by appropriate personnel.	—	X
*CHANGE CONTROL*
5.4.2	Significant changes, which may impact on quality of product stored at warehouse or on regulatory requirements, have to be agreed between SUPPLIER and WLA PHARMASE. A non-exhaustive list of significant changes is provided for reference: ü moving activities to a different building or making major structural alterations to the existing facility ü new or modified equipment which has a direct impact on Product quality and that shall require validation and/or calibration e.g. fridge ü changes to the warehouse management system that impact on WLA PHARMASE Products and/or interfaces with WLA PHARMASE systems ü any changes in the status of the SUPPLIER ´s license resulting from the action by the licensing local Competent Authority ü change of the warehouse temperature control or monitoring system ü a change of Management Representative (responsible person / responsible pharmacist) ü a change of an approved sub-contractor.	—	X
5.4.3	For more significant changes WLA PHARMASE is allowed to exercise the power of formal approval, before change is implemented	—	X
*MAINTENANCE & CALIBRATION*
5.4.4	Once decision to implement the change is approved, changes have to be managed according to change control principles; equipment qualification/system validation has to be repeated/integrated. This includes changes to system functionalities or sw upgrades or equipment modification. As a general principle any modification must be tested before release it	—	X
5.4.5	Critical equipment for the functionality of the warehouse operation should be periodically maintained, according to a predefined maintenance plan. A list of key equipment under preventive maintenance is desirable. Measures shall be in place to prevent unauthorized persons from tampering with equipment	—	X

19.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.4.6	Devices used to control or to monitor environmental condition should be periodically calibrated against a primary standard. A list of instruments under periodic calibration is desirable.	—		X
5.4.7	Alarm levels, detecting excursions from predefined acceptable ranges, shall be regularly tested to ensure adequate functionality. This challenge is required as part of calibration activities.	—		X
5.4.8	Maintenance and calibration activities should be performed by qualified personnel in such a way that the integrity of products is not compromised.	—		X
5.4.9	Adequate records of repair, maintenance and calibration activities for key equipment/instruments shall be made and the results shall be retained. Key equipment would include for example cold stores, monitored intruder alarm and access control systems, refrigerators, thermo hygrometers, or other temperature and humidity recording devices, air handling units and any equipment used in conjunction with the onward supply chain.	—		X
*COMPUTER SYSTEM*
5.4.10	A written, detailed description of the system shall be available (including diagrams where appropriate). This shall be kept up to date. The document shall describe principles, objectives, security measures, system scope and main features, how the computerized system is used and the way it interacts with other systems.		—		X
5.4.11	Access to automated system should be granted by user id and password; user profile should be defined according to role in the organization. Data shall only be entered into the computerized system or amended by user profiles authorized to do so.		—		X
5.4.12	A list of GDP automated system and a written description should be available and maintained updated.		—		X
5.4.13	Stored data shall be checked periodically for accessibility. Regular back should be in place and backup data archived for at least 6 years at a separate secure location.		—		X
5.4.14	A restore procedure should be in place and adopted in case of damage or crash of the system		—		X

20

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.5

DOCUMENTATION

5.5.1	Documentation comprises all written procedures, instructions, contracts, records and data, in paper or in electronic form. Documentation shall be readily available and permit the tracking of relevant operations, including batch traceability, during the Storage and Transportation activities. SUPPLIER shall grant WLA PHARMASE access to the records at any time when deemed necessary by WLA PHARMASE.	—	X
5.5.2	A robust procedure management system shall be in place to assure that: · written procedures are univocally identified and are approved at appropriate level before use · only valid and approved procedures are used · current version of the document is available on the floor (including copies of WLA PHARMASE procedures) · superseded version is removed from workstation · title, nature and purpose of the document is clearly stated · procedure are maintained updated and regularly reviewed (minimum every three years) · original version (signed document) of superseded procedure is archived · all GDP operations are covered by written procedures and executed accordingly.	—	X
5.5.3	Ensure documentation developed internally is written in Italian, is clear and not ambiguous.	—	X
5.5.4	Each employee shall have ready access to all necessary documentation for the tasks executed.	—	X
5.5.5	In case document requires to be filled in manually the adequate space should be available for such entries; in this case records shall be made at the time each operation occurs. In case alteration is necessary it shall be signed and dated; the alteration shall permit the reading of the original information. Where appropriate, the reason for the alteration shall be recorded In general, ensure good documentation practices are followed.	—	X
5.5.6	Record all GDP related activities, where required, (e.g. receipt, inspection, Storage, picking & packing, release, transportation, delivery) in a secure, appropriate format.	—	X
5.5.7	Records used to track goods from receipt to distribution should include the following data as minimum: ü Date ü Identification number ü ü Name and address (of supplier, customer, shippers, consignee and so on as communicated formally in the relevant shipment docs) ü	—	—
5.5.8	Archive Product related documents/records and maintain for at least 7 years. Ensure documentation is readily available in case of need. In particular all documents have to be maintained for 3 months after physical destruction of the last kit for each specific clinical trial.	—	X

21.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.5.9

Documents shall be retained for the period
stated in national legislation but at least 10 years from their creation.

Personal data shall be deleted or
anonymised as soon as their storage is no longer necessary for the purpose of
Storage activities.

—

5.5.10

Implement a system permitting WLA PHARMASE to have access to
the Distribution records, allowing batch traceability, at any time when
deemed necessary by WLA PHARMASE.

—

5.5.11

On request, SUPPLIER shall make available to WLA PHARMASE any
data and/or information related to the Products that WLA PHARMASE shall need for
conducting investigations, compiling reports or regulatory purposes.

—

22.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.6

IMPs MANAGEMENT

5.6.1	IMPs shall be stored separately from other pharmaceutical products shall be protected from the harmful effects of light, temperature, moisture and other external factors. Particular attention shall be paid to products requiring specific storage conditions; cold chain products must be stored in cold room, while non-cold chain products must be stored in the temperature controlled warehouse.	—	X
5.6.2	Incoming containers of medicinal products shall be cleaned, if necessary, before storage.	—	X
5.6.3	Storage operations must ensure appropriate storage conditions are maintained and allow for appropriate security of stocks.	—	X
5.6.4	On regular basis physical removal of unsalable stock should be performed. Those products have to be put in a segregated area (specifically dedicated to non-saleable goods) waiting for disposal.	—	X
5.6.5	Products shall be handled and stored in such a manner as to prevent spillage, breakage, contamination and mix-ups. Products shall not be stored directly on the floor unless the package is designed to allow such storage (such as for some medicinal gas cylinders).	—	X

23.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.7

PRODUCT CERTIFICATION

5.7.1	SUPPLIER shall keep delivery documents to be provided to WLA PHARMASE on request. SUPPLIER shall notify WLA PHARMASE any discrepancy regarding the information expected in delivery documents.	—	X
*INCOMING CHECKS*
5.7.2	SUPPLIER has to follow standard procedures for incoming checks according to GDP/GMP/GCP.	–	X
5.7.3	At arrival, Products are verified to confirm as minimum: Origin (from approved suppliers), Identity (item number and batch number), Quantity, Labelled Storage conditions, Integrity of the packaging (no visible damage). Output of incoming verification must be documented. In case of any non-conformance found during incoming checks SUPPLIER shall inform WLA PHARMASE without delay (1 business day) providing all necessary information and evidence, when applicable.	—	X
5.7.4	Particular attention should be paid to verify shipping conditions. In case of data logger, which accompany deliveries on receipt, SUPPLIER shall verify and document data from temperature device for adherence to expected product storage conditions (as per packing list or similar). If data-logger is not present, obtain from the driver the print out of the truck. When print out are available shipping temperature data must be collected and verified. Products which at arrival do not meet all acceptance criteria will not be considered free for the market and need to be left in pending status till WLA PHARMASE decision.	—	X
5.7.5	SUPPLIER has to provide temperature data . Products which at arrival do not meet all acceptance criteria will not be administered to be left in pending status till WLA PHARMASE decision, as defined in the Work Instructions	—	X
5.7.6	GxP Documents have to be maintained at least for 7 years in particular for IMPs they have to be stored until destruction of all IMPs drug for the specific trial.	—	X
5.7.7	Products requiring special storage or security measures (see cold chain products) shall be prioritized and once appropriate checks have been conducted they shall be immediately transferred to appropriate storage facilities. Incoming checks verification has to be conducted in a way which does not compromise product quality.	—	X

24.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.8	NON-CONFORMING PRODUCTS (including damaged) OR SERVICE
5.8.1	Notify WLA PHARMASE within one business day after notice of deviations to Products or from operational activities that may impact on the quality of the Products or Service provided, such as but not limited to: – any issues relating to the status or expiry date of Product – any damaged stock received or stock damaged in warehouse – warehouse management system deviations that impact on Products and/or interfaces – warehouse environmental conditions deviations / malfunctions that can have impact on product quality – any inventory inaccuracy (e.g. stolen or lost) – any issues where Product Storage or transportation requirements are not met. These examples do not constitute an exhaustive or exclusive list.	—	X
5.8.2	In first instance potential non-conforming Products must be blocked in the warehouse management system, in order they are not available for picking operations. The Quality Assurance contact person(s) at Sponsor/WLA PHARMASE as defined in the Work Instructions has to be informed for instructions on disposition of potential non-conforming Products.	—	X
5.8.3	WLA PHARMASE as defined in the Work Instructions has to evaluate the event and provide feedback to SUPPLIER in written (e-mail).	X	—
5.8.4	If confirmed as non-conforming SUPPLIER shall physically remove from saleable stock the products involved, for further actions (i.e. disposal). When impact on product quality is evident (i.e. broken or damaged units) SUPPLIER is allowed to treat the goods as non-conforming without authorization by Sponsor/WLA PHARMASE as defined in the Work Instructions. Information toHSE as defined in the Work Instructions is anyway required.	—	—

5.9

25. Technical Product Complaints

5.9.1

All technical Product Complaints concerning Products
must have in place an SOP for complaint management. If necessary, appropriate follow-up actions
(including CAPA) shall be taken after investigation and evaluation of the
complaint, including where required notification to the national competent
authorities.

—

5.9.2

Complaints shall be recorded with all the
original details. A distinction shall be made between complaints related to
the quality of a Product and those related to distribution. In the event of a
complaint about the quality of a Product and a potential product defect, the
manufacturer shall be informed without delay.

Any product distribution complaint shall be
thoroughly investigated to identify the origin of or reason for the
complaint.

—

5.10

SELF INSPECTION

5.10.1

SUPPLIER shall conduct and document self-inspections
to assess quality systems.

On yearly basis a self-inspection program must be
issued; audit of subcontractors should be part of the above mentioned
program.

Reports should contain observations and CAPA.

Effective follow up should be performed on CAPA

—

5.11	SUB-CONTRACTING
5.11.1	SUPPLIER shall have in place a procedure for suppliers evaluation and qualification, requiring for periodic audit to those entities.	—	X
5.11.2	In case of services with a potential impact on quality, a contract should be in place between SUPPLIER and ALL service providers. All quality relevant aspects are clearly defined as well as associated responsibilities of the parties involved	—	X
5.11.3	In case SUPPLIER will subcontract one or more services which is covered by the obligations of this QTA, the qualification process of the subcontractor should be successfully completed and documented, before using it. A preliminary audit is required to assess quality system of the supplier.	—	X
5.11.4	In case of a new subcontractor, not included in Attachment 5, audit results are presented to WLA PHARMASE to share conclusion on request.	—	X
5.11.5	An updated list of service suppliers shall be available; GDP relevance of the service provided is desirable.	—	X
5.11.6	As the contract giver SUPPLIER should provide the subcontractor (contract acceptor) all relevant information necessary to perform the contracted activities in accordance with GDP and all applicable requirements.	—	X

26.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.12	27. TRANSPORTATION (GENERAL)
5.12.1	SUPPLIER assures that Products are delivered to designated delivery point, under labelled Storage conditions. In case of dangerous goods transport apply all applicable measures to prevent damage to people, environment or properties The following responsibilities apply as long as the delivery is under SUPPLIER responsibility	—	X
5.12.2	WLA PHARMASE shall provide SUPPLIER all necessary information regarding products storage conditions, and or special instruction for product handling.	X	—
5.12.3	SUPPLIER ensures that adequate precautions are taken against spillage, breakage, contamination by micro-organisms, mix-ups and cross-contamination and that the integrity of the Products is not compromised during all Transportation Activities	—	X
5.12.4	In case a deviation occurs during transportation (temperature excursion, damage, loss, or theft) SUPPLIER must be immediately informed (within the same working day) by its suppliers and all information passed to WLA PHARMASE without any delay (1 business day from receiving the information)	—	X
5.12.5	Sponsor/WLA PHARMASE as defined in the Work Instructions will evaluate the effect of temperature excursion on the product for further action with the customers involved.	X	—

LOADING/UNLOADING

5.12.6

Vehicles and containers should be loaded carefully
and systematically, where applicable on a first-out/last-in basis, to save
time when unloading, to prevent physical damage and to reduce security risks.

Extra care should be taken during loading and unloading
of cartons to avoid damage.

—

5.12.7

Before loading operation SUPPLIER has to assure that
the following criteria are satisfied:

•The vehicle is clean

•Temperature inside the vehicle is aligned with label
storage condition

Evidence of checks must be provided.

—

VEHICLES

5.12.8

SUPPLIER shall use only dedicated vehicles specific
for pharmaceutical transportation.

Goods other than medicinal products are not allowed,
with exception of medical device, food supplements and cosmetics.

Of course promotional or scientific material (paper)
accompanying the delivery is allowed.

—

5.12.9

Vehicles used for transportation of WLA PHARMASE products must be regularly maintained and cleaned, free from litter
and dust, in order to prevent
contamination and exposure of the Products to conditions that could affect
their quality and packaging integrity.

Cleaning and fumigation agents without adverse effect
on the quality of the Product shall be used.

—

5.12.10

Vehicles should comply with national transport
regulations and with current standards. The drivers cab should be separated
from the loading area.

Vehicles should be inspected and maintained on a
regular basis.

—

28.

RESPONSIBILITIES

WLA PHARMASE

SUPPLIER

5.12.11

Vehicles used for transportation of WLA PHARMASE products
must be insulated and temperature controlled trucks, equipped with active
temperature control system, in order to maintain the temperature conditions
suitable for the products.

They must be qualified before use; qualification has
to provide evidence that during transport WLA PHARMASE products are not exposed at
potential risk which can compromise product quality; mapping studies has to
be conducted in order to identify the most appropriate probes positioning and
numbers.

Mapping studies has to be repeated in the alternate
season to challenge the adverse weather conditions

—

5.12.12

SUPPLIER assures that devices used for monitoring
conditions within vehicles and containers (temperature) are calibrated by duly
qualified personnel at regular intervals (once a year minimum) against a
certified reference standard.

Certificate of calibration shall be available on WLA PHARMASE
request (i.e. in case of deviation/investigation)

—

TEMPERATURE DURING TRANSPORTATION

5.12.13

For every delivery it shall be possible to
demonstrate that required storage conditions have been maintained during all
the entire transportation and that therefore products have not been exposed
to temperature conditions which may compromise quality and integrity.

This means that raw data should be available for 100%
of transportation till point of destination (first line client).

On request raw data have to be provided at arrival to
the receiving point.

In case of unavailability of raw data (i.e. run out
of ink or paper; printer broken, ecc) SUPPLIER has to be informed and remote
download of raw data has to be granted anyway.

If no possibility exists to have evidence, WLA PHARMASE must
be informed.

—

DELIVERY MANAGEMENT

5.12.14	Deliveries shall be made to the address stated on the delivery note and into the care or the premises of the consignee. Products shall not be left on alternative premises or outside, exposed to external environment.	—	X
5.12.15	For emergency deliveries outside normal business hours SUPPLIER has to assure that the request received from WLA PHARMASE is addressed with the same level of quality as those during normal business hours.	—	X
5.12.16	WLA PHARMASE must be informed in a timely manner / immediately on any deviations regarding a Product delivery, as delay, undeliverability, damage, non -correct loading or temperature deviations. As far as applicable, SUPPLIER will then start formal investigation and implement corrective and preventive actions to prevent recurrence of the deviation.	—	X
5.12.17	Delivery shall be arranged in a way to minimize the duration of temporary storage while awaiting the next stage of the transportation route	—	X

SECURITY

5.12.18

SUPPLIER assures that all possible and necessary
security measures are adopted during transportation to prevent unauthorized
persons from entering and/or tampering with vehicles, containers and/or
equipment, as well as to prevent the theft or misappropriation thereof.

For instance, GPS system, alarm system, use of seals,
checks on drivers are non-exhaustive example of security measures

—

TRANSIT POINT

5.12.19

Where the transportation route includes unloading and
reloading or stay at an hub (transit point), SUPPLIER shall assure that WLA PHARMASE products
are not exposed to conditions which can represent a risk for quality during
the period of stay at the transition hub. In particular, temperature
conditions, cleanliness, pest control and security must be maintained with an
acceptable level at the intermediate storage facilities (hubs) as reported in
table above.

—

6. LIST OF ATTACHMENTS

Attachment 01	Version	Effective Date
Amendment History	01	effective date of QTA
Amendment History
Attachment 02	Version	Effective Date
Key contact persons	01	effective date of QTA
Key contact persons
Attachment 03	Version	Effective Date
Transit points of Supplier	01	effective date of QTA
Transit points of Supplier
Attachment 04	Version	Effective Date
List of subcontractors	01	effective date of QTA
List of subcontractors

7. SIGNATURES

PREPARED BY:

Raffaella Lamanna_____________________ DATE__________

Global QA Head

ACCEPTED BY:

Name
Function SUPPLIER _____________________ DATE______

ATTACHMENT 1

Version 01

Amendment History

Upon amendment or revision of this QTA or one of the Attachments the revision history shall be updated.

QTA

Amendment No.	Effective Date	Amended Section
01		First Edition

PREPARED BY:

Raffaella Lamanna_________________________ DATE__________

Global QA Head

ACCEPTED BY:

Name
Function SUPPLIER _________________________ DATE_________

ATTACHMENT
2

Version
01

Key contact persons

Key contact persons and their deputies for but not limited to the quality issues and supply chain/logistics issues must be named and specified. If required, a key contact person shall delegate day to day operational instructions to an appropriate deputy provided overall responsibility is retained. This shall be by formal instruction from the key contact person identified below.

WLA PHARMASE
Function	Individual	Phone/Fax	E-mail
Global QA Head	Raffaella Lamanna	+39 03311539409	raffaella.lamanna@WLA PHarmaSE.us.com


SUPPLIER
Function	Individual	Phone/Fax	E-mail

This attachment shall be updated independently from the Quality Agreement.

PREPARED BY:

Raffaella
Lamanna_________________________ DATE __________

Global QA Head

ACCEPTED BY:

Name
Function SUPPLIER_________________________ DATE
__________

ATTACHMENT
3

Version
01

Transit points of SUPPLIER

The activities for the WLA PHARMASE business represented in this Quality Agreement by the SUPPLIER for the Storage of Product have been agreed for the following listed locations operated by the SUPPLIER:

Site name	Address	Type of activity
		Long term Storage	Distribution

This attachment shall be updated independently from the Quality Agreement.

PREPARED BY:

Raffaella
Lamanna_________________________________ DATE __________

Global QA Head

ACCEPTED BY:

Name
Function SUPPLIER _________________________ DATE________

ATTACHMENT
4

Version
01

List of subcontractors

The subcontracting of activities for the WLA PHARMASE business represented in this Quality Agreement by the SUPPLIER for the Storage and Distribution of Product have been agreed for the following listed companies and their associated activity, provided however that such approval shall not be deemed as a limitation of the SUPPLIER’s liability and obligations under the Main Agreement:

List of approved subcontractors:

SUPPLIER
Name of subcontractor	Address (legal head office address)	subcontracting activity


	[A2]

This attachment shall be updated independently from the Quality Agreement.

PREPARED BY:

Raffaella
Lamanna_________________________ DATE __________

Global QA Head

ACCEPTED BY:

Name
Function SUPPLIER _________________________ DATE
_________

[A1]Add your logo please

[A2]Fill in with list of subcontractors

Contact Us:

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Quality Assurance Agreement

1. GENERAL

1. SCOPE

2. ORDER OF PRECEDENCE

3. TERM

4. AMENDMENTS

5. REPORTS

6. REFERENCE

2. DEFINITIONS

3. SUB-CONTRACTING

4. AUDITING

5. TABLE OF RESPONSIBILITIES

7.

8. General

9

10

11. PERSONNEL

12

13

14. TRANSIT-POINTS

15.

16

17.CLEANING AND PEST CONTROL

18

19.

20

21.

22.

23.

24.

25. Technical Product Complaints

26.

27. TRANSPORTATION (GENERAL)

28.

6. LIST OF ATTACHMENTS

7. SIGNATURES

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17.
CLEANING AND PEST CONTROL