Compounding Sterile Preparations 4th Edition Chapter 4 Pharmacy Middlesex University 16 pag Document shared on https www docsity com en compounding sterile preparations 4th edition chapter 4 8990409 Downloaded by kareey winniewangari432 gmail com Chapter 4 Sterile Preparation Formulation Mark G Klang INTRODUCTION This chapter will provide insight into the issues of formulation when applied to compounding sterile preparations The majority of options discussed in this chapter will involve high risk compounding as de ned by USP Chapter 797 Pharmaceutical Compounding Sterile Preparations 1 Also sterile compounding that requires specialized formulations may be designated dif cult to compound by the newly created U S Food and Drug Administration FDA Task Force This group examines specialized formulations and the resources available to pharmacists to safely conduct such procedures This group then decides which modality or therapy is outside the scope of compounding The Pharmacy Compounding Advisory Committee has met several times to evaluate what drug products are exempt from compound ing under both Sections 503A and 503B of the Federal Food Drug and Cosmetic Act In June 2015 the FDA advisory group met to consider adding four more drugs to the list aprotinin ondansetron bromocriptine and acetaminophen The compounder would be prohibited from any form of compounding that includes one of the banned active ingredients 2 Please refer to Chapter 21 for the stability and incompatibility of drugs Chapter 15 for labeling compounded preparations Chapter 16 for documentation Chapter 17 for sterilization methods and Chapter 18 for nished preparation release checks and tests FEDERAL REGULATIONS NEW COMPOUNDING DRUG REGULATIONS The following is an excerpt of an FDA release pertinent to compounding sterile preparations On November 27 2013 President Obama signed the Drug Quality and Security Act DQSA legislation that contains important provisions relating to the oversight of compounding of human drugs Note The author acknowledges E Clyde Buchanan who authored this chapter in the previous edition 51 Document shared on https www docsity com en compounding sterile preparations 4th edition chapter 4 8990409 Downloaded by kareey winniewangari432 gmail com 52 Compounding Sterile Preparations Title I of this new law the Compounding Quality Act removes certain provisions from section 503A of the Federal Food Drug and Cosmetic Act FDCA that were found to be unconstitutional by the U S Supreme Court in 2002 Section 503A describes the conditions under which certain compounded human drug products are exempt from three sections of the FDCA requiring cid 127 Compliance with current good manu facturing practices CGMPs section 501 a 2 B cid 127 Labeling with adequate directions for use section 502 f 1 and cid 127 FDA approval prior to marketing sec tion 505 The new law creates also a new section 503B in the FDCA Under section 503B a compounder can become an outsourcing facility An outsourcing facility will be able to qualify for exemptions from the FDA approval requirements and the requirement to label products with adequate directions for use but not the exemption from CGMP requirements Outsourcing facilities cid 127 Must comply with CGMP requirements cid 127 Will be inspected by FDA according to a risk based schedule and cid 127 Must meet certain other conditions such as reporting adverse events and providing FDA with certain information about the products they compound 3 When formulating and compounding sterile prepa rations pharmacists must follow both state laws and FDA regulations State pharmacy practice acts and board of pharmacy regulations cover these activities The FDA also regulates formulation and compounding under adulteration misbranding and new drug provisions of the FDA 4 Since 1980 in their Field Regulatory Guidance Hospital Pharmacies Status as Drug Manufacturer FDA Guide 7132 06 states that a physician may prescribe an unusual preparation that requires compounding by a pharmacist from drugs readily available for other uses and which is not generally regarded as safe and effective for the intended use 5 If the pharmacy lls each prescription as received clearance under the new drug provisions is not required 5 Compounding Phase 1 investigational drugs does not require full compliance with CGMPs because of the low volume of patients 6 Compounding medications for Phase II and III trials requires complete adherence to CGMPs and products prepared for Phase I cannot be used for the subsequent phases if not prepared under full CGMPs If a pharmacist compounds nished drugs from bulk active ingredients that are not obtained from an FDA approved facility or are not compliant with compendial standards i e The United States Pharmacopeia and The National Formulary USP NF these nished preparations must be covered by a new drug application 7 In other words bulk compounded preparations must conform to USP Chapter 795 Pharmaceutical Compounding Nonsterile Preparations and USP Chapter 797 otherwise FDA requires that a new drug applica tion be led and accepted for the bulk compounded preparation 1 If a pharmacist changes the strength dosage form or components of a commercially available preparation in a compounded prescription good compounding procedures should be used 7 Pharma cists are responsible for compounding and dispens ing nished preparations pursuant to prescribed therapy and for compounding and preparing those preparations in compliance with established boards of pharmacy and other regulatory agencies These requirements vary from state to state PROFESSIONAL STANDARDS Formulating compounding and sterilizing a pharmaceutical from nonsterile ingredients or in nonsterile containers is the most dif cult and is considered a high risk procedure 1 The chemical purity and content strength of ingredients must meet their original or compendial speci cations in unopened or in opened packages of bulk ingredients in compliance with the Ingredient Section of USP Chapter 795 8 Batch master worksheets should include comparisons of actual with anticipated Document shared on https www docsity com en compounding sterile preparations 4th edition chapter 4 8990409 Downloaded by kareey winniewangari432 gmail com yields sterilization methods and quality control and validation of procedures used Presterilized sealed containers should be used when feasible Final containers must be sterile and capable of maintaining product integrity