Active pharmaceutical ingredients manufacturing

Active Pharmaceutical Ingredients Committee (APIC) (1999), Cleaning validation in active pharmaceutical ingredient manufacturing plants, APIC. 

W.E. Hall, Cleaning for active pharmaceutical ingredient manufacturing facilities. In I.R., Berry, D. Harpaz, (eds.). Validation of Active Pharmaceutical Ingredients. 2nd ed. IHS Health Group, 2001. 

Table 9 Application of Good Manufacturing Practice to Active Pharmaceutical Ingredient Manufacturing... 

Table 8.9 Application of good manufacturing practice to active pharmaceutical ingredient manufacturing.

Sterile processing facilities require additional levels of sophistication. Active pharmaceutical ingredients manufactured for sterile use are required to be completed (usually the isolation/purification steps) in a sterile facility. The sterile facility is designed to minimize the exposure of the product from microbial contamination. 

These and other FDA policy decisions launched the pharmaceutical industry and academia into a new era of developing stereoselective processes for the manufacture of enantiopure active pharmaceutical ingredients (APIs). 

Draft Guidance for Industry on Manufacturing, Processing, or Holding Active Pharmaceutical Ingredients Availability Notice, Fed Regist. Docket No. 98-0193, 1998. 

Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients... 

Annex 18 Good manufacturing practice for active pharmaceutical ingredients (The ICH Guide) Annex 19 Reference and Retention Samples... 

Thomas, P.W. and Ramsay, A. (2004) Continuous manufacturing of a bulk active pharmaceutical ingredient. Presented at Switching from Batch to Continuous Processing Conference,... 

PIC, 1987, Guidelines for the Manufacture of Active Pharmaceutical Ingredients (Bulk Drug Substances) (Document PH 2/87). 

Tab. 14.1 The role ofGMP (good manufacturing practice) in the production and processing of APIs (active pharmaceutical ingredients) from difference sources. It is not yet clear how biotechnology-derived plants fit into this scheme. Modified from the Good Manufacturing Practice Guide for Active Pharmacuetical Ingreedients, ICH (2000).

The pharmaceutical industry produces between 25 and 100 kg or more of waste for every kilogram of active pharmaceutical ingredient (API) manufactured.1 According to a leading practitioner of the industry, the potential waste coproduced with APIs is in the range of 500 million to 2 billion kg per year. Even at a nominal disposal cost of 1 per kg, the potential savings just in waste avoidance is significant faced to the pharmaceutical industry annual sales (almost 500 billion in 2003). 2... 

The design of crystallization processes for the manufacture of Active Pharmaceutical Ingredients is a significant technical challenge to Process Research and Development groups throughout the Pharmaceutical and related industries. It requires an understanding of both the thermodynamic and kinetic aspects of crystallization, to ensure that the physical properties of the product will consistently meet specification. Failure to address these issues may lead to production problems associated with crystal size, shape and solubility, and to dissolution and bioavailability effects in the formulated product. 

The Committee for Proprietary Medicinal Products [8] applied the BCS, with certain requirements, to dispense with bioequivalency tests if the active pharmaceutical ingredient is class I and the in vitro dissolution of the finished dosage form is fast [9], An active substance is considered highly soluble if the amount contained in the HDS of an IR product is dissolved in 250 ml of each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0, 4.6, and 6.8). There should be linear and complete absorption, which indicates HP to reduce the possibility of an IR dosage form influencing the bioavailability [8], The similarity of the dissolution profiles of the test and reference products is demonstrated in each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0,4.6, and 6.8). If there is rapid dissolution of the product, where at least 85% of the active substance is dissolved within 15 min, no further comparison of the test and reference is required. Further requirements include that excipients be well established and have no interaction with the pharmacokinetics of the active substance and that the method of manufacture of finished product... 

The Guidance applies to the manufacture of active pharmaceutical ingredients (APIs) for use in human drug products. It is detailed in Table 9.1. 

Source Adapted from International Conference for Harmonization. Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, ICH Q7,2000. 

Safety Production of the requisite drug molecule, called the active pharmaceutical ingredient (API) or bulk pharmaceutical chemical (BPC), may involve materials, solvents, or intermediates that are volatile, toxic, or even explosive. The development program has to determine the appropriate manufacturing processes to ensure that safety is not compromised and the API can be produced and purified to remove impurities and toxic residues. 

CDER web site http //www.fda.gov/cder. A complete section is dedicated to the Internationally Harmonised Guide for Active Pharmaceutical Ingredients (API) and Good Manufacturing Practice (GMP), Washington, Sept. 1997. 

K. Morris, U. Griesser, C. Eckhardt and J. Stowell, Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes, Adv. Drug Delivery Rev., 48(1), 91-114 (2001). 

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, ICH Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, 2000. 

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