4. Glossary:
The definitions given below apply to the terms as used in these guidelines. They may have different meanings in other contexts.
Active Pharmaceutical Ingredient (API):
Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical dosage form and that, when so used, becomes an active ingredient of that pharmaceutical dosage form. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.
Comparator Product:
The comparator product is a pharmaceutical product with which the multisource product is intended to be interchangeable in clinical practice. The comparator product will normally be the innovator product for which efficacy, safety and quality have been established. The selection of the comparator product is usually made at the national level by the medicines regulatory authority.(For the WHO Prequalification of Medicines Programme, the selection of the comparator product is based on the information presented under Guidance on bioequivalence studies available on the Prequalification web site.)
Control Strategy:
A planned set of controls, derived from current product and process understanding that ensures process performance and product quality. The controls can include parameters and attributes related to active pharmaceutical ingredient and finished pharmaceutical product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control.
Critical Process Parameter (CPP):
A process parameter whose variability has an impact on a critical quality attribute and, therefore, should be monitored or controlled to ensure the process produces the desired quality.
Critical Quality Attribute (CQA):
A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range or distribution to ensure the desired product quality.
Finished Pharmaceutical Product (FPP):
A finished dosage form of a pharmaceutical product, which has undergone all stages of manufacture, including packaging in its final container and labeling.
Fixed-Dose Combination Finished Pharmaceutical Product (FDC-FPP):
A finished pharmaceutical product that contains two or more active pharmaceutical ingredients.
Formal Experimental Design:
A structured, organized method for determining the relationship between factors affecting a process and the output of that process. Also known as “design of experiments”.
Generic Product:
See multi source (generic) pharmaceutical products.
Life-Cycle:
All phases in the life of a product from the initial development through marketing until the product’s discontinuation.
Multi source (generic) Pharmaceutical Products:
Multi source pharmaceutical products are pharmaceutically equivalent or pharmaceutically alternative products that may or may not be therapeutically equivalent. Multisource pharmaceutical products that are therapeutically equivalent are interchangeable.
Pharmaceutical Alternatives:
Products are pharmaceutical alternative(s) if they contain the same molar amount of the same active pharmaceutical moiety(s) but differ in dosage form (e.g. tablets versus capsules), and/or chemical form (e.g. different salts, different esters). Pharmaceutical alternatives deliver the same active moiety
by the same route of administration but are otherwise not pharmaceutically equivalent. They may or may not be bioequivalent or therapeutically equivalent to the comparator product.
Pharmaceutical Equivalence:
Products are pharmaceutical equivalents if they contain the same molar amount of the same active pharmaceutical ingredient(s) in the same dosage form, if they meet comparable standards, and if they are intended to be administered by the same route. Pharmaceutical equivalence does not necessarily imply therapeutic equivalence, as differences in the excipients and/or the manufacturing process
and some other variables can lead to differences in product performance.
Pharmaceutical Product:
Any preparation for human or veterinary use that is intended to modify or explore physiological systems or pathological states for the benefit of the recipient.
Pilot-Scale Batch:
A batch of an active pharmaceutical ingredient or finished pharmaceutical product manufactured by a procedure fully representative of and simulating that to be applied to a full production-scale batch. For example, for solid oral dosage forms, a pilot scale is generally, at a minimum, one-tenth that of a full production scale or 100 000 tablets or capsules, whichever is the larger; unless otherwise adequately justified.
Primary Batch:
A batch of an active pharmaceutical ingredient or finished pharmaceutical product used in a stability study, from which stability data are submitted in a registration application for the purpose of establishing a retest period or shelf life, as the case may be.
Process Robustness:
Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality.
Production Batch:
A batch of an active pharmaceutical ingredient or finished pharmaceutical product manufactured at production scale by using production equipment in a production facility as specified in the application.
Quality:
The suitability of either an active pharmaceutical ingredient or a pharmaceutical product for its intended use. This term includes such attributes as the identity, strength and purity.
Quality Target Product Profile (QTPP):
A prospective summary of the quality characteristics of a finished pharmaceutical product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the finished pharmaceutical product.
Stringent Regulatory Authority (SRA):
For the purpose of this document, a stringent regulatory authority (SRA) is the medicines regulatory authority in a country which is:
■ (a) A member of the International Conference on Harmonisation
of Technical Requirements for Registration of Pharmaceuticals for
Human Use (ICH) (European Union, Japan and the United States of
America); or (b) an ICH Observer, being the European Free Trade
Association as represented by SwissMedic and Health Canada (as
may be updated from time to time); or (c) a regulatory authority
associated with an ICH member through a legally binding, mutual
recognition agreement including Australia, Iceland, Liechtenstein
and Norway (as may be updated from time to time);
■ Only in relation to good manufacturing practices inspections: a
medicines regulatory authority that is a member of the Pharmaceutical
Inspection Co-operation Scheme as specified at http://www.
picscheme.org.
Therapeutic Equivalence:
Two pharmaceutical products are considered to be therapeutically equivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and after administration in the same molar dose, their effects, with respect to both efficacy and safety, are essentially the same when administered to patients by the same route under the conditions specified in the labelling. This can be demonstrated by appropriate bioequivalence studies, such as pharmacokinetic, pharmacodynamic, clinical or in vitro studies.
Pharmaceutical Development of Multi source (generic) Finished Pharmaceutical Products – points to consider, (Annex 3, WHO Technical Report Series 970, 2012)
