Market Actions Policy at a GMP Site

Market Action Procedure shall be available at each GMP site that produces, stores or distributes Drug Products, Active Pharmaceutical Ingredients (API) or Medical Device and within each Business Unit responsible for any Market Action activities.

The Market Action procedure must be capable of being initiated promptly and at any time. The procedure shall include an outline of actions required to address the following Market Action types as they apply to the markets involved:

– Product Recall,

– Market Withdrawal, and/or

– Field Correction.

Although this procedure applies globally, it is recognized that different and additional local regulatory requirements may exist. In all such instances, the local regulatory requirements are to take precedence and local Site procedures shall encompass such requirements.

Any site employee who becomes aware of a situation that might require a Market Action shall report the matter at once to a Supervisor, who shall inform any member of the Site Quality Team or of the Area Quality Review Team.

Site Management shall be notified of all significant issues that will or might result in a Market Action

A Market Action Leader shall be identified to coordinate activities necessary to implement a Market Action. A Market Action Leader shall be appointed to represent each country in which the Market Action is conducted. This person must have responsibilities in Regulatory Affairs or Quality Operations and be knowledgeable in the Market Action process and interactions with Regulatory Authorities.

For recalls conducted in the US and its territories, a Market Action Coordination Committee (MACC) shall be identified. The MACC at a minimum shall consist of the following responsible Center Function principals:

– Market Action Leader;

– Quality Operations;

– Medical Affairs;

– Regulatory Affairs;

– Distribution/Logistics;

– Marketing;

– Country General Counsel (Legal); and

– Media Relations (if information releases are involved).

For market actions conducted in countries outside the US, activities necessary to implement the market action shall be coordinated by the Market Action Leader for each country (e.g. country Regulatory Affairs principals or Business Unit Quality Contact) with assistance from the GMP Site Quality Team.

The Quality Team at the Site responsible for manufacturing the product responsible for the contract manufacturer shall be notified of market actions, conducted in countries outside the US for imported products that are initiated due to local Regulatory Team requirements.

The concerned Country Regulatory Affairs Managers and Country Qualified Person(s) (QP) shall be informed of and/or involved in any contact or interactions with the country regulatory authorities.

The Recommendation to Initiate a Market Action, shall be made by the Site Quality Team. The recommendations shall be confirmed in writing by the team meeting minutes.

For Market Actions in the US, the Market Action Coordination Committee (MACC) shall make the decision whether or not to initiate a Market Action.

For Market Actions in countries outside the US, the country Regulatory Affairs principals or Business Unit Quality Contact shall make the decision whether or not to initiate a Market Action.

If the Site Quality Operation (QO) Leader decides to recall a batch (e.g.for personal liability reasons) the decision cannot be overruled by Marketing principals.

Notification by a Regulatory Team can cause a Market Action to be initiated. In such an event, Site communication with the Regulatory Team shall be through Regulatory Affairs principals and/or the responsible Site Quality Team or Qualified Person (QP). The concerned Country Regulatory Affairs Managers and Country Qualified Person(s) shall be informed of and/or involved in any contact or interactions with the country regulatory authorities.

Initiation of a Market Action occurs at the time a decision is made that either a Product Recall, a Market Withdrawal, or a Field Correction is required.

When the Decision to Initiate a Market Action is Made in the US or its Territories, notification of the Market Action shall be made through QSTS principals via issuance of the MACC minutes or memorandum.

When a Decision to Initiate a Market Action is Made, Affecting Countries Outside of the US or its Territories, the responsible, Quality Operations Regional Leader (QORL), or Contract Operations Quality Assurance (COQA) Leader, or QSTS representative shall issue a Global Notification to inform the responsible principals representing, at least, the following functions:

– Quality Operations;

– Regulatory Affairs (RA);

– Medical Affairs;

– In Europe, Business Unit Quality Contacts and EU Pharmacovigilance QP, for Market Actions; and

– Other senior management principals (Marketing, Country General Counsel, Sales, Distribution/Logistics, and Supply Chain Management).

Upon receipt of the Global Notification, each country RA principal and/or Business Unit Quality Contact shall decide if additional notifications to country Regulatory Authorities are required. This decision shall be documented in accordance with local regulatory requirements.

If a Market Action will result in an interruption to the supply chain, the relevant country Regulatory Authorities shall be notified by the country RA principal and/or Business Unit Quality Contact.

Periodic Reports of the Market Action Status, when required by regulations, shall also be issued to inform the Regulatory Authorities of the Market Action progress. The Market Action Leader shall ensure that a Final Report of the Market Action, including reconciliation between the delivered and recovered quantities of product, shall be prepared, when required by regulations.

Site Principals shall periodically evaluate the effectiveness of, and preparations for implementing the Market Action procedure by conducting a mock Market Action to Verify adequacy of their local procedure and training of related personnel. Mock Market Actions shall be performed in accordance with a time period specified in the Site’s local procedure, unless a real Market Action had occurred in the same specified time period. Records of such evaluations and audits shall be maintained.

For human health products marketed in the US and its territories, QSTS shall assume responsibility for performing a mock recall when required.

A Specific Market Action Strategy shall be prepared by the Market Action Leader(s) for each Market Action initiated, defining actions to be taken in each affected country. The Market Action Strategy must include, at least, the following:

– Type of Market Action;

– Depth (i.e., level of product distribution) of the Market Action (e.g., wholesale, retail / pharmacy, patient);

– Classification of the Market Action based on the potential health risk;

– Method of customer or public notifications; and

– Extent of Market Action Effectiveness Checks, if required by regulations.

The Market Action Leader(s) shall also arrange for this strategy to be reviewed and Approved by the Regulatory Team when required by regulations.

The Seriousness of a Potential Health Hazard is determined by Medical Affairs and/or Safety principals and is communicated to the country RA principals, who will provide the information to the impacted country Regulatory Authorities for consideration in classifying a Product Recall.

Accurate, Detailed Inventory and Distribution Records of APIs, medical devices, and drug product Lots or Batches must be made readily available to the MACC or, Country Regulatory Affairs Manager or Business Unit Quality Contact to facilitate a Market Action. Responsibility for providing this information to these principals lies with the personnel responsible for managing Distribution / Logistics Services, Depots, and Supply Points.

Product Lots Involved in a Market Action must be physically isolated and placed in designated areas. Final responsibility for lot/batch Disposition is vested with the Site Quality Team.

For Contract Manufacturers Involved in a Market Action, the Director/Team Leader Contract Operations Quality Assurance and/or the responsible Site Quality Team shall serve as the primary liaison between the responsible Market Action Leaders and the contract manufacturer.

When Public Information Releases are required, a draft shall be sent to the applicable Country General Counsel (Legal), Regulatory Affairs, Business Unit Quality Contact, Marketing, Medical Affairs, and Media Relations for review and authorization.

Effectiveness Checks, when required by regulations, shall be conducted to verify that customers have received Market Action notifications and have taken the specified action.

A Market Action Final Report shall be prepared by the Market Action Leader and issued as defined by the Market Action Procedure at the completion of the Market Action to, at least, the following:

– Regulatory Authorities; and

– Responsible management principals [e.g., Quality Operations, Regulatory Affairs, Medical Affairs, Qualified Person (QP), Marketing, Country General Counsel].

Market Actions shall be considered in a number of situations including, but not limited to, the following:

– Results of a Product Complaint Investigation,

– Review of product retention samples of a distributed product lot,

– Material erroneously released to stock without Quality Team authorization,

– Mislabeled marketed product,

– Failure of a marketed product lot to meet Specifications, or

– Request or mandate from a Regulatory Team.

When a Potential Market Action is Identified, a Stop Distribution Notice (SDN) shall be issued for all affected lots and the affected lots shall be placed under Quarantine-Hold status.

The Market Action Leader in conjunction with the Site Quality Team is responsible to ensure the following activities are completed:

– Inform and/or involve the concerned Country Regulatory Affairs Managers and Country Qualified Person(s) in relevant Market Action activities.

– Consultation with Regulatory Authorities, in country of manufacture and country of distribution, on Market Action activity.

– Identification of the product and Lot Numbers involved and the time period when the affected lot(s) was/were distributed.

– Preparation of the draft Market Action communication.

– Preparation of the draft public information releases for review by applicable Country General Counsel (Legal), Regulatory Affairs, Business Unit Quality Contact, Marketing, Medical Affairs, and Media Relations,

– Notification of Site Global Research and Development principles of Market Actions, which could affect clinical studies.

– Coordination of Market Action communications.

– Determination of the depth (i.e., level of product distribution) of the Market Action (e.g., wholesale, retail/pharmacy, patient).

– Verification that a complete record of all returned material is maintained by the receiving locations.

– Determination of the method and level of Effectiveness Checks, as required;

– Preparation of all status reports, where required and final reports related to the Market Action.

– Maintenance of records of all Site-related Market Actions in accordance with established record retention standards and procedures.

– Verification of proper disposition of returned product.

– Coordination and/or execution of Effectiveness Checks as required.

Country or Area Medical Affairs and/or Safety Representatives shall assess the health and safety risks associated with the product being
considered for a Market Action and shall advise the responsible Market Action Leader and country RA principals.

Factors to be considered bythe Medical Affairs and/or Safety representative include, and are not limited to, the following:

– Whether any disease or injuries have already occurred from the use of the product.

– Whether any existing conditions could contribute to a clinical situation that could expose humans or animals to a health hazard.

– Assessment of the likelihood of occurrence of the hazard.

– Assessment of the ability to detect the issue prior to use.

– Assessment of the hazard to various segments of the population (e.g., children, surgical patients) who are expected to be exposed to the product.

– Assessment of the degree of seriousness of the health hazard;

– Assessment of the consequences (immediate or long term) of the occurrence of the hazard.

– Assessment of whether any potential injury or impairment is permanent or reversible.

Personnel responsible for Managing Distribution/ Logistics Services, Depots and Supply Points shall determine the following information and providing it to the responsible Market Action Leader:

– Quantity of the impacted product in stock and in distribution;

– First and last dates of distribution; and

– Names and addresses of customers at each distribution Site (for US Market Actions only).

Inventory Records shall be current, clear, and accurate and shall contain, at least, the following:

– Name and strength of the product,

– Description of the product,

– Name and address of the customer,

– Date and quantity shipped,

– Lot or control numbers involved,

– Quantity of product in distribution, and

– First and last dates of distribution at each distribution Site.

Market Action Communications to Customers shall:

– Be brief and to the point;

– State that the product in question is subject to a Market Action;

– Identify clearly the product, lot quantity, lot numbers, codes or serial numbers, and other pertinent descriptive information to enable accurate and immediate identification of the affected product;

– Explain concisely the reason for the Market Action including potential hazard involved, if any;

– Indicate that further distribution or use of any remaining product should cease immediately;

– Specify whether the customers are required to further notify their customers who received the product; and

– Provide specific instructions on what should be done with the products involved and a ready means for the recipients of the communication to report as to the quantity of the product in their possession (e.g., a postage-paid, self-addressed postcard).

The Following Market Action Documents shall be provided to Regulatory Authorities by Regulatory Affairs or the responsible Quality Team, when required by regulations:

– Market Action Notifications,

– Market Action Status Reports,

– Market Action Follow-up Reports, and

– Market Action Final Reports.

The Market Action Final Report shall include at least, the following:

– Drug product, medical device, or API identification;

– Market Action required;

– Quantities distributed;

– Quantities returned;

– Final disposition of drug product, medical device or API;

– Date the Market Action closed; and

– Approval signature.

Market Action Final reports for recalls conducted in the US shall also include:

– Number of customers contacted and date contacted, and

– Number of customers that responded.