Annex 1 of the EU GMP Guide is currently being revised and will take into account the updated ISO standard. In the meantime, for the qualification or requalification of cleanroom facilities, pharmaceutical manufacturers may apply the updated ISO standard with reference to Annex C (macroparticle counting) or continue to follow the previous ISO standard. However, routine surveillance should continue to be conducted in accordance with the existing Schedule 1. In principle, a GMP declaration can only be revoked after a re-examination by an EU authority, which leads to the issuance of a GMP certificate. In practice, this can lead to difficulties for manufacturers established in third countries. All procedures performed to obtain the final product of high quality must be recorded. After receiving the raw materials from production to actual sale, the company must record everything. GMP requires the use of good documentation processes (GDP), which are part of the requirements of the quality management system. Records should document all GMP activities with appropriate review and approval. GDP means that documents must be: sampling plans and procedures must be statistically valid. They should be based on scientifically sound sampling methods.
You should also consider the risk associated with accepting defective products (based on the predetermined classification of defects, the criticality of the material, and the seller`s quality history). This ensures that the end result obtained from raw data is based on good science and that any data exclusion or change in processing method is based on good science. Visibility of all processing information provides protection against undisclosed “compliant processing.” This edition reflects recent regulatory changes, clarifies existing requirements, addresses industry FAQs and includes an updated list of appendices. This procedure should indicate that samples must be taken from each batch of sterilizers, including the coolest location identified when the sterilizer is qualified. The number of samples per batch shall be determined on the basis of a risk-based approach and the total number of samples per batch shall comply with the requirements of the European Pharmacopoeia set out in point 2.6.1.3. Another option, which would require an amendment to the relevant existing authorisations, would be to introduce a parametric release system, which would eliminate the need to perform the sterility test. Physical treatment such as grinding an active pharmaceutical ingredient would not constitute PMI production. Similarly, the principles set out above could be applied to allow the exchange of audit reports between different manufacturing authorisation holders using the same active substance supplier, provided that it can be demonstrated that the scope of the audits is applicable to active substances of common interest. Pharmaceutical manufacturers and distributors are good examples. The quality of each batch remains the same throughout the process – from ingredient testing to packaging and labeling of the final product, they must consistently meet standards.
Importers of pharmaceutical products must have proof of GMP compliance at their premises in Canada of foreign buildings where API is manufactured, packaged, labelled and tested. For more information, refer to Health Canada`s document entitled How to Demonstrate Compliance of Foreign Buildings with Good Manufacturing Practices for Drugs (GUI-0080). Note: For the purposes of these guidelines, this definition also includes: an active substance used in the manufacture of a drug of non-biological origin and listed in Schedule C to the Act. Any form of mixing or transformation of the active substance with other substances would also require a manufacturing authorisation for the IMP if the resulting product is to be used in a clinical trial. The outcome of your quality risk management process should help you determine the need for and extent to which space and equipment should be dedicated to a particular product or product family. This may include the assignment of specific product contact parts or the entire production facility. It may be acceptable to limit manufacturing activities to a separate, self-contained production area within a multi-product plant if you can justify it. EU authorities are aware that these documents are also used to support applications for authorisation in third countries and that sometimes various additional requirements, including copies of apostilles, are expected. Given the integrity of entries in the EudraGMDP database, EU authorities strongly encourage the use of the database.
In cases where a suspected quality defect affects several production sites, reporting obligations should be laid down in a technical agreement. It is common practice that the placing on the market and the place of final certification of EU batches play a prominent role in notification, unless otherwise justified. The European Medicines Agency (EMA) provides answers to frequently asked questions on Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP), as discussed and approved by the Working Group of GMP/GDP Inspectors. A concern for inspectors is when the lot numbers for the bulk product and the finished product are completely different and there is no obvious link between the two. Although the manufacturer has a traceability system in place, inspectors agree that this is an undesirable practice that should be avoided.