This article defines the requirements for the Disposition of materials used and products produced, at GMP sites involving:
- Drug Products including Validation and demonstration Batches.
- Active Pharmaceutical Ingredients (API) including validation and demonstration batches
- Raw Materials (RM);
- API Starting Materials;
- Intermediates;
- In-Process Materials;
- Medical Devices;
- Packaging Materials; and
- Other Materials.
The Site Quality Team shall be responsible for establishing a system for assigning a disposition to materials in accordance to local regulatory requirements and the requirements of this local business. This system shall include, but is not limited to, the following:
- Applicable Material Control Documents (MCD);
- Compendial Specifications, where applicable; and
- Review of associated documentation [e.g., Certificate of Analysis (COA), batch Records, Device History Record (DHR) and Certificate ofCompliance].
- Material status indication has to be addressed.
Standard Operating Procedures (SOP) shall be established at each site to describe the disposition processes for all materials and products used or produced at the Site.
The Receiving GMP Site Quality Team shall assign the disposition of the APIs, drug products, and medical devices manufactured, tested, packaged or held under contract by a Contract Vendor, unless the Quality Agreement specifies the contract vendor has team to assign the disposition to the products.
An Investigation shall be conducted for failure of a batch/Lot of material to meet specifications or for a Deviation from an Approved Production, testing, or distribution procedure.
Each Batch/Lot of Production Materials, APIs, Drug Products, Medical Devices and Reprocessed or Reworked Materials shall meet, as a minimum standard, Regulatory Specifications (RS) to be approved and released for use.
Disposition of Production Materials Intended for Use with Drug Products, APIs, or Medical Devices, Tested by the Supplier, and Supplied to GMP site with a COA, shall conform to local regulatory requirements and minimally include:
An identity test performed by the site; and Periodic (at least annually) confirmation of supplier test results.
Hazardous or highly toxic incoming materials may be released based on the
supplier’s certificate of analysis without an identification test. The rationale for not performing the identification test must be documented and approved by the Site Quality Team.When such materials are intended for use in manufacture of medical devices, requirements include:
- An inspection performed by the site; and
- Periodic (at least annual) confirmation of supplier test results.
In-Process Materials shall be approved by the Quality Team at significant phases during the production process and before proceeding to the next manufacturing step, unless a delay in holding the material would adversely impact the drug product or medical device. Intermediates can be
approved by the Production Team for use in the next manufacturing step provided that the batch production records of Critical Process Steps are reviewed and approved by the Site Quality Team before the API batch is released or distributed.
Disposition of APIs, Drug Products, and Medical Devices by the Site Quality Team shall include a review and assessment of batch manufacturing, packaging, and testing records to assure the records are complete and accurate.
Disposition of medical devices shall also include a review of batch/lot documentation to ensure that all activities required by the Device Master Record (DMR) have been completed.
The Site Quality Team shall also review the following information associated with the production of a batch:
- Deviation investigation reports [e.g., Laboratory Investigation Report (LIR) and Quality Deviation Report (DR) have been completed and approved
- Any applicable change control;
- Correct Expiration Date or Re-evaluation Interval has been assigned to the finished product; and
- Results from examination of the final finished pack, when required.
In Addition to the Requirements in this article, Disposition of Sterile APIs, Sterile Drug Products and Sterile Medical Devices shall include a review of environmental and personnel monitoring records.
The Product Disposition shall be documented, signed (written or electronic), and dated by the Quality Team representative making the disposition decision, and included in the batch record or DHR. Such dispositions include, but are not limited to, the following:
– Approved,
– Quarantine,
– Quarantine-Hold,
– Acceptable for Rework/Reclaim, and
– Rejected.
In addition to the above items, the disposition shall also document the actual quantity of materials being assigned the disposition.
If Only a Portion of the Batch or Lot is to be Approved, the quantity of the material that was assigned a disposition other than approved (e.g., Quarantined-Hold, Acceptable for Rework/Reclaim or Rejected) shall be verified to have been segregated from the portion of the batch or lot that is to be approved prior to the approval of the rest of the batch or lot.
For Prospective Validation, validation reports must be approved prior to product release and distribution of validation batches in accordance with the established site validation requirements.
A Quality Agreement with a Contract Vendor shall specify the requirements for approval of products produced by the contract vendor.
The duties of the Qualified Person(s) include ensuring:
- Each batch of medicinal products manufactured within the European Community have been produced and tested/checked in accordance with the local regulatory directives and the marketing authorisation.
- For medicinal products manufactured outside the European Community, a Qualified Person must ensure that each imported batch has undergone, in the importing country required testing.
