Quality Control

Quality Control

Quality Control Is most Important part of Quality Team. Quality Control Department is deal with Sampling, Specification & Analytical Procedure preparation & appropriate execution.Quality Control department is also 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 satisfactory.

As per EudraLex – Volume 4 – Good Manufacturing Practice ( GMP ) Guideline.

  • Each holder of a manufacturing authorisation should have a Quality Control Department. This department should be independent from other departments, and under the authority of a person with appropriate qualifications and experience, who has one or several control laboratories at his disposal. Adequate resources must be available to ensure that all the Quality Control arrangements are effectively and reliably carried out.
  • The principal duties of the head of Quality Control are summarised in Chapter 2. The Quality Control Department as a whole will also have other duties, such as to establish, validate and implement all quality control procedures, oversee the control of the reference and/or retention samples of materials and products when applicable, ensure the correct labelling of containers of materials and products, ensure the monitoring of the stability of the products, participate in the investigation of complaints related to the quality of the product, etc. All these operations should be carried out in accordance with written procedures and, where necessary, recorded.
  • Finished product assessment should embrace all relevant factors, including production conditions, results of in-process testing, a review of manufacturing (including packaging) documentation, compliance with Finished Product Specification and examination of the final finished pack.
  • Quality Control personnel should have access to production areas for sampling and investigation as appropriate.

GLP (Good Laboratory Practice ) in Quality control.

  • Quality Control Laboratory Area & equipment should meet the general & Specific Requirements for Quality Control Areas given in Chapter 3. Laboratory equipment should not be routinely  moved between high risk areas to avoid accidental Cross-Contamination.
  • In particular the microbiological laboratory should be arranged so as to minimise risk of Cross-Contamination.
  • the personnel  premises, and equipment in the laboratories should be appropriate to the tasks imposed by the nature and the scale of the manufacturing operations. The use of outside laboratories, in conformity with the principles detailed in Chapter 7, Contract Analysis, can be accepted for particular reasons, but this should be stated in the Quality Control records.

Documentation of Quality control Department.

Minimum Availability in of Documents In Quality control department as per given below ;

  • Specifications.
  • SOP for Sampling, Testing, Records ( Including test worksheets & Laboratory  notebooks format ), Recording and verifying ;
  • SOP for calibration/qualification of instruments and Maintenance of Equipment also department should maintain Records of the same.
  • SOP of investigation of out of specification and out of Trend results.
  • testing reports and/or certificates of analysis.
  • Data from environmental (air,water & other utilities ) monitoring, where required;
  • validation records of test methods where is applicable.

Laboratory Inspection

The specific objective will be spelled out prior to the inspection. The laboratory inspection may be limited to specific issues, or the inspection may encompass a comprehensive evaluation of the laboratory’s compliance with CGMP’s. As a minimum, each pharmaceutical quality control laboratory should receive a comprehensive GMP evaluation each two years as part of the statutory inspection obligation.

In general these inspections may include

  • the specific methodology which will be used to test a new product

  • a complete assessment of laboratory’s conformance with GMP’s

  • a specific aspect of laboratory operations

Activity of Quality Control Department


Evaluate the company’s system to investigate laboratory test failures. These investigations represent a key issue in deciding whether a product may be released or rejected and form the basis for retesting, and resampling.

In a recent court decision the judge used the term “out-of-specification” (OOS) laboratory result rather than the term “product failure” which is more common to FDA investigators and analysts. He ruled that an OOS result identified as a laboratory error by a failure investigation or an outlier test. The court provided explicit limitations on the use of outlier tests and these are discussed in a later segment of this document., or overcome by retesting. The court ruled on the use of retesting which is covered in a later segment of this document. is not a product failure. OOS results fall into three categories:

  • laboratory error

  • non-process related or operator error

  • process related or manufacturing process error


An OOS laboratory result can be overcome (invalidated) when laboratory error has been documented. However, non-process and process related errors resulting from operators making mistakes, equipment (other than laboratory equipment) malfunctions, or a manufacturing process that is fundamentally deficient, such as an improper mixing time, represent product failures.

Examine the results of investigations using the guidance in section 5 above and evaluate the decision to release, retest, or rework products.


Evaluate the company’s retesting SOP for compliance with scientifically sound and appropriate procedures. A very important ruling in one recent court decision sets forth a procedure to govern the retesting program. This district court ruling provides an excellent guide to use in evaluating some aspects of a pharmaceutical laboratory, but should not be considered as law, regulation or binding legal precedent. The court ruled that a firm should have a predetermined testing procedure and it should consider a point at which testing ends and the product is evaluated. If results are not satisfactory, the product is rejected.


Firms cannot rely on resampling. The court ordered the recall of one batch of product after having concluded that a successful resample result alone cannot invalidate an initial OOS result. to release a product that has failed testing and retesting unless the failure investigation discloses evidence that the original sample is not representative or was improperly prepared.

Evaluate each resampling activity for compliance with this guidance.


Averaging can be a rational and valid approach when the object under consideration is total product assay, but as a general rule this practice should be avoided. The court ruled that the firm must recall a batch that was released for content uniformity on the basis of averaged test results. because averages hide the variability among individual test results. This phenomenon is particularly troubling if testing generates both OOS and passing individual results which when averaged are within specification. Here, relying on the average figure without examining and explaining the individual OOS results is highly misleading and unacceptable.

Content uniformity and dissolution results never should be averaged to obtain a passing value.

In the case of microbiological turbidimetric and plate assays an average is preferred by the USP. In this case, it is good practice to include OOS results in the average unless an outlier test (microbiological assays) suggests the OOS is an anomaly.


The laboratory serves a vital function in blend testing which is necessary to increase the likelihood of detecting inferior batches. Blend uniformity testing cannot be waived in favor of total reliance on finished product testing because finished product testing is limited.


The review of microbiological data on applicable dosage forms is best performed by the microbiologist (analyst). Data that should be reviewed include preservative effectiveness testing, bioburden data, and product specific microbiological testing and methods.

Review bioburden (before filtration and/or sterilization) from both an endotoxin and sterility perspective. For drug substance labs evaluate methods validation and raw data for sterility, endotoxin testing, environmental monitoring, and filter and filtration validation. Also, evaluate the methods used to test and establish bioburdens.

Refer to the Microbiological Inspection Guide for additional information concerning the inspection of microbiological laboratories.


Review personal analytical notebooks kept by the analysts in the laboratory and compare them with the worksheets and general lab notebooks and records. Be prepared to examine all records and worksheets for accuracy and authenticity and to verify that raw data are retained to support the conclusions found in laboratory results.

Review laboratory logs for the sequence of analysis versus the sequence of manufacturing dates. Test dates should correspond to the dates when the sample should have been in the laboratory. If there is a computer data base, determine the protocols for making changes to the data. There should be an audit trail for changes to data.


Ascertain that suitable standards are being used (i.e. in-date, stored properly). Check for the reuse of stock solutions without assuring their stability. Stock solutions are frequently stored in the laboratory refrigerator. Examine the laboratory refrigerators for these solutions and when found check for appropriate identification. Review records of standard solution preparation to assure complete and accurate documentation. It is highly unlikely that a firm can “accurately and consistently weigh” to the same microgram. Therefore data showing this level of standardization or pattern is suspect and should be carefully investigated.


Information regarding the validation of methods should be carefully evaluated for completeness, accuracy and reliability. In particular, if a compendial method exists, but the firm chooses to use an alternate method instead, they must compare the two and demonstrate that the in-house method is equivalent or superior to the official procedure. For compendial methods firms must demonstrate that the method works under the actual conditions of use.

Methods can be validated in a number of ways. Methods appearing in the USP are considered validated and they are considered validated if part of an approved ANDA. Also a company can conduct a validation study on their method. System suitability data alone is insufficient for and does not constitute method validation.


Laboratory equipment usage, maintenance, calibration logs, repair records, and maintenance SOPs also should be examined. The existence of the equipment specified in the analytical methods should be confirmed and its condition noted. Verify that the equipment was present and in good working order at the time the batches were analyzed. Determine whether equipment is being used properly.

In addition, verify that the equipment in any application was in good working order when it was listed as used to produce clinical or biobatches. One would have to suspect the data that are generated from a piece of equipment that is known to be defective. Therefore, continuing to use and release product on the basis of such equipment represents a serious violation of CGMP’s.


Some inspections include the coverage of the manufacturer of the drug substance. The safety and efficacy of the finished dosage form is largely dependent on the purity and quality of the bulk active drug substance. Examine the raw data reflecting the analysis of the drug substance including purity tests, charts, etc.

Check the impurity profiles of the BPC used in the biobatch and clinical production batches to determine if it is the same as that being used to manufacture full scale production batches. Determine if the manufacturer has a program to audit the certificate of analysis of the BPC, and, if so, check the results of these tests. Report findings where there is substantial difference in impurity profiles and other test results.


Evaluate the test results from in-process tests performed in the production areas or laboratory for conformance with established sampling and testing protocols, analytical methods, and specifications. For example, evaluate the tests for weight variation, hardness, and friability. These tests may be performed every fifteen or thirty minutes during tableting or encapsulating procedures. All testing must comply with CGMP’s.


A stability-indicating method must be used to test the samples of the batch. If there is no stability-indicating assay additional assay procedures such as TLC should be used to supplement the general assay method. Evidence that the method is stability indicating must be presented, even for compendial methods.


The use of computerized laboratory data acquisition systems is not new and is addressed in the following CGMP guidance documents:

– Compliance Policy Guide 7132a.07 Computerized Drug Processing: Input/Output Checking.

– Compliance Policy Guide 7132a.08 Computerized Drug Processing: Identification of “Persons” on Batch Production and Control Records.

– Compliance Policy Guide 7132a.11 Computerized Drug Processing: CGMP Applicability to Hardware and Software

– Compliance Policy Guide 7132a.12 Computerized Drug Processing: Vendor Responsibility

– Compliance Policy Guide 7132a.15 Computerized Drug Processing: Source Code for Process Control Application Programs

– Guide to Inspection of Computerized Systems in Drug Processing.


Overall management of the laboratory work, its staff, and the evaluation of the results of analysis are important elements in the evaluation of a control laboratory. Span of supervisory control, personnel qualifications, turnover of analysts, and scope of the laboratory’s responsibility are important issues to examine when determining the quality of overall management and supervision of work. Individually or collectively, these factors are the basis for an objection only when they are shown to result in inadequate performance of responsibilities required by the CGMPs.


EudraLex – Volume 4 &

Pharmaceutical Quality Control Labs (7/93)(USFDA)


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