ipc

• In-process control


  A standard component of the QA/QC systems throughout the pharmaceutical manufacturing
• Why in-process control is important

  • To check consistency of the product
• Weigh in process product

  Weight of all the products
• In-process control activities


  1. Sampling

  2. Testing

  3. Inspection after every significant stage of the manufacturing process
• Test for deliverable volume

  Prior to filling liquid/product to the bottle
• Finished packages shall be checked throughout the run at regular intervals
• Frequency of in-process checking

  For high tech and newer machines, check every hour. For manual process or primitive machines, check every 30 mins.<|>After a power outage, in-process checking should be done
• Written procedures for in-process control

  1. Specs to be checked (consistent w/ FP specs)

  2. Limits of acceptability of each spec determined by the application of suitable statistical methods
• Test results outside the acceptable limits indicate a process variation problem either in the manufacturing or analytical procedures, which should be investigated and corrected
• Results of in-process test shall be recorded to become part of the batch record
• WI's should define the procedure to follow & on how to utilize the inspection & test data to control the process
• Out-of- specification (OOS) investigations
• Sampling for in-process materials

  Specified sample size<|>Prescribe an increased sampling rate where in-process materials do not appear to be homogeneous<|>Specify the extent of collection of samples for chemical tests - Frequency of sampling
• If there is not a good distribution of active ingredient, there is also not a good distribution of dosage strength
• In-process testing


  Product Name<|>Batch / Lot No.<|>Tests to be conducted: identity: strength; purity and quality as appropriate<|>The in-process specs shall be consistent w/ the FP specs
• In-process control tests for tablets

  1. Granules: moisture content determination, sieve (screen analysis) to determine particle size distribution

  2. Compression: individual weight determination, average unit weight determination, diameter, disintegration test
• Friability test


  • Ability of the tablet to withstand abrasion in packaging, handling, and shipping. Requirement: should not be more than 1.0%
• Hardness test


  • Measures the degree of force required to break a tablet. Requirement: varies per product; usually between 4.0kg/ cm2 and 9.0 kg/ cm2
• Tablet thickness


  • Can vary with no change in weight due to: (1) difference in the density of the granulation, (2) pressure applied to the tablets, and (3) speed of tablet compression. Determined with a caliper or thickness gauge. A plus or minus 5% may be allowed depending on the size of the tablet
• Physical defects in tablets

  • Contaminations, capping, mottling or non-homogeneous distribution of colour, lamination, picking, sticking
• In-process control tests for syrups/liquid preparations

  Clarity & completeness of solution, color, flavor, pH, specific gravity, viscosity, homogeneity, final batch volume
• In-process control tests for capsules

  Average unit weight, individual unit weight, disintegration time
• In-process control tests for creams, ointments, semi-solids

  Appearance, homogeneity, colour, odour, pH (excluding ointments), viscosity of cream, final batch weight
• When determining the frequency of sampling & testing, consideration should be given to the precision of machine, speed of the process, and batch size
• The determination of tolerance limits & in-process material specifications should be derived from the best result obtained from previous acceptable batches and should be consistent with the finished product specifications
• Due considerations should be given to experimental results obtained for the mean and standard deviation in determining the realistic specification limits
• 20 tablets = not more than 6% relative standard deviation. If 10 tabs not more than 2% if 6 not more than 3%
• In-Process Control is therefore important to ensure batch uniformity & integrity of the product
• PICS/GMP Requirement for Finished Product Specification


  The designated name of the product and the code reference where applicable<|>The formula<|>A description of the pharmaceutical form and package details<|>Directions for sampling and testing<|>The qualitative and quantitative requirements, with the acceptance limits<|>The storage conditions and any special handling precautions, where applicable<|>The shelf-life
• MONOGRAPH- USP NF
• Finished Product Specifications (FPS)


  Critical quality standards that are a list of tests, references to analytical procedures and appropriate acceptance criteria (numerical range or limit)
• Conforms to Specification


  Means that the drug product (formulated preparation), when tested to the analytical procedures, will meet the listed acceptance criteria
• Categories of specifications


  Intended use<|>Different acceptance criteria for release testing and stability testing
• Compendia


  A collection or compilation of drug or drug products monographs
• United States Pharmacopeial Convention (USP)


  A scientific nonprofit organization that sets standards for quality, purity, identity and strengths of medicines, food ingredients and dietary supplements manufactured, distributed and consumed worldwide. Enforce in US FDA, also used by more than 130 countries. Published twice a year. Have 4000 monographs. USP contains drug substances and drug products monographs. NF contains excipients monographs.
• European Pharmacopeia Commission


  Establishes official standards that provide a legal and scientific basis for quality control during development, production and marketing of medicines in 37 signatory states. Published every three years with supplements. Have 2000 monographs including chemical substances, antibiotics, vaccines, dosage forms, herbal products and homeopathic preparations.
• British Pharmacopeia


  The official collection of standards for UK medicinal products and pharmaceutical substances. Published every year. Have 3000 monographs.
• Japanese Pharmacopeia


  Provides an official standard to ensure the quality if medicines in Japan.
• Monograph


  A written standard that describes an article (e.g. drug substance, drug product, excipient, compounded preparation), which provides the name of substances, its definition, package and storage, labeling requirements, information on tests needed to ensure the substances is of appropriate identity, strength, quality and purity.
• Why there's no toxicology in monographs? Lahat ng precaution sa monograph it is a precaution that the substance will not be toxic to other people. Indicated na yung maximum dosage and maximum storage condition kapag nag go beyond ka dun, dun sya magiging toxic.