Manufacturing Consideration of Sterile

Pharmaceutical Products

Summary of Study
The increased understanding of the product and process as well as advances in technology may
enable improvements in control strategies or changes to the manufacturing process parameters.
From a regulatory standpoint, the phrase continual improvement suggests enhancement of
quality.
Pharmaceutical product development and commercial manufacturing are subject to government
regulation and oversight in virtually every country. This oversight includes review and approval
of new products and site inspection for quality management (CGMP) of pharmaceutical
production, packaging, storage, and distribution facilities. Regulatory authorities charged with
oversight of the pharmaceutical industry have limited resources with which to carry out their
mission. As the pharmaceutical industry continues to grow and globalize, the issue of the
resources available to regulatory authorities has become more critical. Many regulatory
authorities have addressed the resources problem by introducing risk based inspectional systems
in which each facility is rated for relative risk and inspectional resources are preferentially
directed to those facilities with high manufacturing risk profiles. For example, the European
Medicines Agency (EMA) uses an assessment of Site Complexity, Process Complexity, and
Product Complexity to generate an overall risk profile for a given facility.
Sterile products are high risk because product failure generally has serious health consequences.
For some governments their responsibilities extend to individual products in addition to the
overall state of compliance of the industry. Countries that institute an Essential Medicine List
(EML) must source EML products for use in the healthcare system. This raises the question of
product quality based risk assessment in determining that individual sources of supply to
government of EML products are in compliance and producing product that is fit for use.

Introduction
Sterile products are dosage form of therapeutic agents that are free of viable microorganisms.
Principally, these include parenteral, ophthalmic and irrigating preparations. Of these, parenteral
products are unique among dosage forms of drug because they injected through the skin or
mucous membranes into internal body compartments. Thus because they have circumvented the
highly efficient first line of body defense, the skin and mucous membranes, they must be free
from microbial contamination and from toxic components as well as posses an exceptionally
high level of purity. All components and processes involved in the preparation of these products
must be selected and designed to eliminate, as much as possible, contamination of all types,
whether of physical, chemical, or microbiological origin (Avis,1987).
The preparation of sterile parenteral products requires careful control of all ingredients,
materials, and processes to ensure the final product has the identity and strength, and meets the
quality and purity characteristics that it purports to possess. Contamination affecting these
critical properties of parenteral products can occur in many ways and from many sources (Lewis
et al.,2010).
Quality by design (QbD) and process analytical technology (PAT) have become priorities for the
Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA).
Numerous recent initiatives within CDER and FDA have had the objective of encouraging the
pharmaceutical industry to utilize QbD and PAT in their product development and manufacturing
processes. Although sterile products may be a minority compared to non-sterile dosage forms
(e.g., solid orals), their absolute requirement for sterility make design and control of the
manufacturing processes extremely critical. This emphasis on the manufacturing process makes
the sterile drug product an obvious target for QbD and PAT (Riley and Li,2011).

Consideration for sterile products manufacturing

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General considerations
Quality control
Sanitation
Environmental Monitoring
Manufacture of sterile preparations
Sterilization
Terminal sterilization
Aseptic processing and sterilization by filtration
Isolator technology
10. Blow/fill/seal technology
11.Personnel
12. Premises
13. Equipment
14. Finishing of sterile products