GMP manufacturing

The first requirement for GMP manufacture is the availability of trained personnel. Other requirements are as follows  

An environment should have appropriate controls for temperature, pressure, and relative humidity. For aseptic production, cleanroom conditions monitored for particles and bioburden contamination are necessary. Equipment must be validated and maintained with current calibration. Processes must be developed and validated to ensure the production of pure and consistent product. 

Operating procedures must be clearly written down, detailing each manufacturing step. 

Approved batch records must be kept for registering all relevant information during the manufacturing process. 

QC tests are carried out according to validated analytical methods or established methods from pharmacopoeias US Pharmacopoeia and British Pharmacopoeia. Exhibit 10.2 lists some of the QC analytical methods performed on drug intermediates and products. 

Chapter 10 Good Manufacturing Practice Drug Manufacturing 

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The manufacture of all investigational medicinal products (including placebo) that are intended for a clinical trial must be authorised and conducted according to Good Manufacturing Practice (GMP). This should be supervised and certified by a Qualified Person . An import authorisation is required for any product from outside the EU, which should also be manufactured to GMP standards. (See Ghapters 11 and 12 for information on GMP, manufacturing authorisations and Qualified Persons.)... 

Abridged National Authorization Procedure This procedure is for generics, and there is no necessity to provide preclinical or clinical results. However, evidence of bioavailability and bioequivalence and GMP manufacturing compliance has to be submitted. If the applicant has an abridged approval from a member state, the Mutual Recognition Procedure can be used. 

The United States, the European Union, and Japan have implemented this GMP Guidance, and the details are presented in Exhibit 9.3. The Q7 GMP Guidance sets out the requirements for GMP manufacturing. Details are summarized in Exhibit 9.4. Most of the requirements of ICH Q7 are derived from... 

Personnel engaged in GMP manufacturing of drug products are required to be formally trained in quality practices. They are only assigned to tasks for which they have been trained. This is to guarantee that drugs are manufactured by qualified personnel and quality is built into each step of the manufacturing process. 

DQ is performed by the supplier of the equipment or system at the supplier s factory as part of the factory acceptance test (FAT). IQ (based on site acceptance test—SAT), OQ, and PQ are performed on-site at the GMP facility. For a GMP manufacturing facility, the validation activities include the facility design, FTVAC system, environment control, laboratory and production equipment, water system, gases and utilities, cleaning, and analytical methods. Validation protocols (IQ, QQ, and PQ) are prepared for each item, listing all critical steps and acceptance criteria. Deviations are reviewed and resolved before the validation activity proceeds to the next phase. 

Generally, GMP manufacturers use compendial methods from the US Pharmacopoeia, British Pharmacopoeia, or European Pharmacopoeia as much as possible for analyses and testing purposes, as these methods have been validated and accepted by regulatory authorities. However, manufacturers are... 

What are the benefits for the implementation of a risk-based approach in GMP manufacturing ... 

Cole, D. L. (1999). Keynote address—GMP manufacturing of antisense oligonucleotides at Isis Pharmaceuticals for clinical trials and the marketplace Yesterday, today and tomorrow. IBC Conf. Oligonucleotide Pept. Manuf. Strategies, San Diego, CA, 1999. 

Avoiding the need to establish and maintain a GMP manufacturing facility ... 

Most El-deficient recombinant adenoviruses are propagated in the HEK-293 and PER.C6 cell lines (and derivatives thereof) as discussed in Section 10.1.2.3. The generation of RCAs is minimal in PER.C6 but remains a concern for HEK-293. Both cell lines have been documented for GMP manufacturing [110]. The production of these cells can be accomplished by a variety of methods, which depend on whether adherent or suspension cell lines are being used. 

Validation Concepts for Computer Systems Used in the USA GMP Manufacture of Drug Products USA GMP PMA s Computer System Validation Committee (Pharm. Technol. May 1986, pp. 24-34) PI (N) 1986... 

BrachySil 1, 3 Brachytherapy 1 Clinical trials 3 GMP manufacturing 2 Hepatocellular carcinoma 3 OncoSil 5 Pancreatic cancer 1 Porous silicon, in brachytherapy 5 Stain etching 2... 

While a non-GMP plant is ready for operation directly after completion of commissioning, for a GMP plant it will take another 6-12 months to establish operational readiness due to facility and equipment qualification and process validation requirements. In addition, for commercial GMP manufacture, and depending on the target markets, the facility needs to be approved by national and international health authorities. 

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