PHARMACEUTICAL QUALITY

In English the word “quality” has several meanings: Nature or characteristic of something Excellence Compliance with a specification Fit-for-purpose Totality of features and characteristics that affect its ability to satisfy a given need

Pharmaceutical Quality: What is meant by “pharmaceutical quality” Inter-relationships of “Quality assurance”, “Quality control” “Good Pharmaceutical Manufacturing practices” Pharmaceutical quality standards How to achieve pharmaceutical quality How to demonstrate pharmaceutical quality.

Orange guide definition “The totality of its attributes and properties which bear upon its fitness for its intended purpose”. In simpler terms Pharmaceutical Quality means producing medicines that consistently act in the manner intended and which are sufficiently pure i.e. they do not contain contaminants, including biological contaminants, that will harm patients.

Thus, quality of pharmaceuticals is not strictly about excellence Thus, quality of pharmaceuticals is not strictly about excellence. For example, it may be possible to make different grades of a drug substance, e.g. having different levels of impurities, 0.5% and 0.05%, the latter being more expensive to produce. If the grade with the higher level is safe and efficacious (as determined in appropriate toxicity and clinical studies), it will be “fit for the purpose” and there is no need to produce the grade having the lower levels of impurities. However, the purer grade may be necessary for injectable dosage forms. It is therefore necessary to define the use of the article before setting the quality standard.

Quality assurance (QA) QA is defined as “a wide ranging concept which covers all matters which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use”. Difference in the meaning of the words: “Assurance” which means “certainty” or “guarantee” or “freedom from doubt” “insurance” which means financial protection against an event which may or may not happen.

Quality Assurance aims to guarantee quality of the pharmaceuticals. "The objectives of Quality Assurance are achieved when processes have been defined which, when followed, will yield a product that complies with its specification, and when the finished product: a. contains the correct ingredients in the correct proportions, b. has been correctly processed, according to the defined procedures, c. is of the purity required, d. is enclosed in its proper container, which bears the correct label (or is otherwise suitably marked or identified), and f. is stored, distributed and subsequently handled so that its quality is maintained throughout its designated or expected life."

Good Manufacturing Practice (GMP) This is defined as “that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by their Marketing Authorisation or product specification. GMP is thus concerned with both production and quality control”. The basic requirements of Good Manufacturing Practice are that: All manufacturing processes should be clearly defined, and known to be capable of achieving the desired ends. All necessary facilities are provided, including: appropriately trained personnel, adequate premises and space,

suitable equipment and services, correct materials, containers and labels, approved procedures (including cleaning procedures), suitable storage and transport. Procedures are written in instructional form, in clear and unambiguous language, and are specifically applicable to the facilities provided Operators are trained to carry out the procedures correctly. Records are made during manufacture (including packaging) which demonstrate that all the steps required by the defined procedures were, in fact , taken and that the quantity and quality produced were those expected. Records of manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a legible and accessible form. A system is available to recall from sale or supply any batch or product, should that become necessary.

Quality Control (QC) Is defined as “that part of Good Manufacturing Practice which is concerned with sampling, specifications and testing and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory”. To achieve effective control of Quality : Adequate facilities and staff should be available for sampling, inspecting and testing starting materials, packaging materials, intermediate, bulk and finished products. Samples of starting materials, packaging materials, and of intermediate products, bulk products, finished products should only be taken by, and methods approved by the person responsible for Quality Control.

Results of the inspection and testing of materials, and of intermediate, bulk or finished products should be formally assessed against specification by the person responsible for Quality Control (Qualified Person - or a person designated by her/him) before products are released for sale or supply. Product assessment should include a review and evaluation of relevant manufacturing (including packaging) documentation. Sufficient reference samples of starting materials and products should be retained (the latter, where possible, in the final pack) to permit future examination if necessary.

Analysis and Testing Testing. The term “test” is used to include all types of objective measurements or characterisations carried out on the sample. Analysis. The term “analysis” is used to mean the determination of the qualitative and/or quantitative composition of a sample by means of appropriate tests, e.g. impurities test, assay. The term “test” is used in a wider context than “analysis” and is applied, for example, to dissolution test, hardness test, preservative efficacy test, bacterial endotoxin test. Thus, the term “test” applies not only to analytical tests but also to tests that determine other characteristics or performance of the material

Relationships between QA, GMP, QC and testing Quality assurance Analysis and testing GMP QC

Quality Management sometimes referred to as Total Quality Management or TQM “The manufacturer shall establish and implement an effective pharmaceutical quality assurance system involving the active participation of the management and personnel of the different services involved”. TQM must be applied at all stages in the lifecycle of the medicine: Research and development of the active ingredient and the formulated product Production of the active ingredient and excipients for marketed products (primary manufacture) Production of the medicinal products (secondary manufacture).

Validation Validation involves demonstrating that any procedure, process, equipment, material, activity or system actually leads to the expected results. Thus all mixers, stirrers, sterilisation procedures, analytical procedures, manufacturing processes etc must be validated and be shown to yield batches that are consistently of the required quality. Pharmaceutical Documentation A very important aspect of GMP is Pharmaceutical Documentation where everything that should be done and everything that has been done is written down. “if it isn’t written down, it is only a rumour”.

Documents may be of the type: Quality manual which contains statements about the policies and standards adopted by the company to achieve the required quality. This usually includes a statement to the fact that the company works to the quality standards laid down by the National and international regulatory authorities. Master formula which is a document showing the composition of the batch. Standard Operating Procedures (SOPs) which provide clear instructions to staff for every step of the manufacturing and testing process. SOPs usually incorporate both instructions and spaces for operators to insert information such as weights, dates, times, batch numbers and/or bar codes, temperatures, machine numbers, any special comments and the name and signature of the operator to indicate that the step was conducted correctly and the date on which it was completed.

Also, there should be a space for the process supervisor to enter her/his name and sign to confirm that she/he has checked the work of the operator. Standard operating procedures must be written for every step, however small, and must give full details of how the material is to be processed, including all stages from raw material to finished product. Records are kept of everything that is done, e.g. records demonstrating that calibration of processing and analytical equipment has been carried out at the correct time, together with the results. records of each batch of medicine. The signed and annotated SOP (see above) becomes part of the batch record, which must accompany the material wherever it goes after the process. Extra sheets of SOPs are usually added to a batch record as the batch progresses through the factory as each process is conducted and completed until the batch has finished processing and lies in the quarantine store awaiting final release approval by the Qualified Person. Training records for all staff, which demonstrate that staff have received appropriate training in every task they undertake (see 2b (i) above).

Qualified Person (QP) Every batch of a medicine must be approved for release onto the market by a Qualified Person who has legal responsibility for ensuring that the batch has been manufactured according to legal requirements, the terms of the Product Licence and the standards of GMP. The QP must examine the batch records of each batch of product before “signing off” the batch. Conclusion The quality of pharmaceutical products thus lies with in the team effort and complying the internal (manufacturer), national and international regulatory and quality standards. A quality product is achieved by the acceptance by everyone involved in pharmaceutical production that attaining the required quality of the medicine is essential for the protection of the health of people who take medicines.