DMF is a document prepared by a pharmaceutical manufacturer and submitted solely at its
discretion to the appropriate regulatory authority in the intended drug market. There is no regulatory requirement to file a DMF. However, the document provides the regulatory authority with confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Typically, a DMF is filed when two or more firms work in partnership on developing or manufacturing a drug product. The DMF filing allows a firm to protect its intellectual property from its partner while complying with regulatory requirements for disclosure of processing details.
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 60 Interpretation of QC analytical data
Quality Control (QC) is an important task in the pharmaceutical industry. It not only protects the manufacturer against compensation claims, but also guarantees the patient a safe and effective product. QC measurements include stability testing of the drug formulation, dissolution testing and analysis of raw materials and synthesis products. Pharmaceutical quality control testing is usually a matter of repetitive testing of samples of APIs or of a limited number of pharmaceutical products. Quality control laboratories may perform some or all quality control activities, e.g. sampling, testing of APIs, excipients, packaging materials and/ or pharmaceutical products, stability testing, testing against specifications and investigative testing. For the quality of a medicine sample to be correctly assessed:
• The submission of a sample of an API, excipient or pharmaceutical product or a suspected counterfeit material to the laboratory, selected in accordance with national requirements, should be accompanied by a statement of the reason why the analysis has been requested. • The analysis should be correctly planned and meticulously executed.
• The results should be competently evaluated to determine whether the sample complies with the specifications or other relevant criteria.
Important QC parameters and definitions
Acceptance criterion for an analytical result: Predefined and documented indicators by
which a result is considered to be within the limit(s) or to exceed the limit(s) indicated in the specification.
Accuracy: The degree of agreement of test results with the true value or the closeness of the
results obtained by the procedure to the true value.
Active pharmaceutical ingredient (API): Any substance or mixture of substances intended to
be used in the manufacture of a pharmaceutical dosage form and that, when so used, becomes an active ingredient of that pharmaceutical dosage form. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.
Analytical test report: An analytical test report usually includes a description of the test
procedure(s) employed, results of the analysis, discussion and conclusions and/or recommendations for one or more samples submitted for testing.
Analytical worksheet: A printed form, an analytical workbook or electronic means (e-
records) for recording information about the sample, as well as reagents and solvents used, test procedure applied, calculations made, results and any other relevant information or comments.
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 61 Batch (or lot): A defined quantity of starting material, packaging material or product
processed in a single process or series of processes so that it is expected to be homogeneous. It may sometimes be necessary to divide a batch into a number of sub-batches which are later brought together to form a final homogeneous batch. In the case of terminal sterilization the batch size is determined by the capacity of the autoclave. In continuous manufacture the batch should correspond to a defined fraction of the production, characterized by its intended homogeneity. The batch size can be defined either as a fixed quantity or as the amount produced in a fixed time interval.
Batch number (or lot number): A distinctive combination of numbers and/or letters which
uniquely identifies a batch on the labels, its batch records and corresponding certificates of analysis.
Calibration: The set of operations that establish, under specified conditions, the relationship
between values indicated by an instrument or system for measuring (especially weighing), recording and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established.
Certificate of analysis: The list of test procedures applied to a particular sample with the
results obtained and the acceptance criteria applied. It indicates whether or not the sample complies with the specification.
Compliance testing: Analysis of active pharmaceutical ingredients (APIs), pharmaceutical
excipients, packaging material or pharmaceutical products according to the requirements of a pharmacopoeial monograph or a specification in an approved marketing authorization.
Control sample: A sample used for testing the continued accuracy and precision of the
procedure. It should have a matrix similar to that of the samples to be analyzed. It has an assigned value with its associated uncertainty.
Design qualification (DQ): Documented collection of activities that define the functional and
operational specifications of the instrument and criteria for selection of the vendor, based on the intended purpose of the instrument.
Good manufacturing practice(s) (GMP): That part of quality assurance which ensures that
pharmaceutical products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.
Installation qualification (IQ): The performance of tests to ensure that the analytical
equipment used in a laboratory is correctly installed and operates in accordance with established specifications.
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 62 Manufacturer: A company that carries out operations such as production, packaging, testing,
repackaging, labeling and/or relabeling of pharmaceuticals.
Marketing authorization (product license, registration certificate): A legal document issued
by the competent medicines regulatory authority that authorizes the marketing or free distribution of a pharmaceutical product in the respective country after evaluation for safety, efficacy and quality. In terms of quality it establishes inter alia the detailed composition and formulation of the pharmaceutical product and the quality requirements for the product and its ingredients. It also includes details of packaging, labeling, storage conditions, shelf-life and approved conditions of use.
Operational qualification (OQ): Documented verification that the analytical equipment
performs as intended over all anticipated operating ranges.
Performance qualification (PQ): Documented verification that the analytical equipment
operates consistently and gives reproducibility within the defined specifications and parameters for prolonged periods.
Pharmaceutical excipient: A substance, other than the active pharmaceutical ingredient
(API), which has been appropriately evaluated for safety and is included in a medicines delivery system to:
— aid in the processing of the medicines delivery system during its manufacture; — protect, support or enhance stability, bioavailability or patient acceptability; — assist in pharmaceutical product identification; or
— enhance any other attribute of the overall safety and effectiveness of the medicine during its storage or use.
Pharmaceutical product: Any material or product intended for human or veterinary use,
presented in its finished dosage form or as a starting material for use in such a dosage form, which is subject to control by pharmaceutical legislation in the exporting state and/or the importing state.
Precision: The degree of agreement among individual results when the procedure is applied
repeatedly to multiple samplings of a homogeneous sample. Precision, usually expressed as relative standard deviation, may be considered at three levels: repeatability (precision under the same operating conditions over a short period of time), intermediate precision (within laboratory variations — different days, different analysts or different equipment) and reproducibility (precision between laboratories).
Primary reference substance (or standard): A substance that is widely acknowledged to
possess the appropriate qualities within a specified context, and whose assigned content is accepted without requiring comparison with another chemical substance.
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 63 Qualification of equipment: Action of proving and documenting that any analytical
equipment complies with the required specifications and performs suitably for its intended purpose.
Quality control: All measures taken, including the setting of specifications, sampling, testing
and analytical clearance, to ensure that raw materials, intermediates, packaging materials and finished pharmaceutical products conform with established specifications for identity, strength, purity and other characteristics.
Quality unit(s): An organizational unit, independent of production, which fulfills both quality
assurance and quality control responsibilities. This can be in the form of separate quality assurance and quality control or a single individual or group, depending on the size and structure of the organization.
Reference material: Material sufficiently homogeneous and stable with respect to one or
more specified properties, which has been established to be fi t for its intended use in a measurement process.
Reference substance (or standard): An authenticated, uniform material that is intended for
use in specified chemical and physical tests, in which its properties are compared with those of the product under examination, and which possesses a degree of purity adequate for its intended use.
Secondary reference substance (or standard): A substance whose characteristics are
assigned and/or calibrated by comparison with a primary reference substance. The extent of characterization and testing of a secondary reference substance may be less
Specification: A list of detailed requirements (acceptance criteria for the prescribed test
procedures) with which the substance or pharmaceutical product has to conform to ensure suitable quality.
System suitability test: A test which is performed to ensure that the analytical procedure
fulfills the acceptance criteria which had been established during the validation of the procedure. This test is performed before starting the analytical procedure and is to be repeated regularly, as appropriate, throughout the analytical run to ensure that the system’s performance is acceptable at the time of the test.
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 64 C. Communication in Pharmaceutical Industry and Regulatory Affairs
Lecture 15. Communication with Regulatory Body
Guidance for Industry -Submission of Clinical Trial Application for Evaluating Safety and Efficacy, Requirements for permission of New Drugs Approval, Post approval changes in biological products, Preparation of the Quality Information for Drug
Guidance for Industry
Submission of Clinical Trial Application to DGDA for Evaluating Safety and Efficacy
All new vaccine and biological products first time produced in Bangladesh from novel seed materials must undergo clinical trials in Bangladesh. Sponsors are required to submit a status report on the clinical trial to the Licensing Authority at the prescribed periodicity. The summary report should provide a brief description of the study, the number of patients exposed to the drug, dose and duration of exposure, details of adverse drug reactions, if any, and the reason for discontinuation of the study or non-pursuit of the new drug application. Any expected serious adverse event (SAE) occurring during a clinical trial should be communicated promptly (within 24 hours and not more than in 14 calendar days) by the Sponsor to the Licensing Authority and to the other Investigator(s) participating in the study.
NOTE: Submit two hard copies and two soft copies i.e. CD’s (PDF format).
Hard copies: It must be well labeled with document number, name of the firm, date of
submission etc. Number of volumes to be labeled as Volume No. / Total number of volumes e.g. if there are five volumes, volume three will be labeled as Volume: 3/5.
Soft Copies: They must be well labeled with document number, name of the firm, date of
submission etc. Scanned copies of signed document like test reports are acceptable as soft copies rest of the documents should be in PDF format. The table of content under each head should be linked to the files (s) or relevant document for easy tracking in CD’s. The table of content should be hyper-linked to the main document to facilitate the review process. Manufacturer should preserve/maintain one hard copy and soft copy of submitted documents in his safe custody for any future reference, if required.
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 65 C. Communication in Pharmaceutical Industry and Regulatory Affairs
Lecture 16. Communication with Regulatory Body
Line up: Submission for New Drug, Communication with DCC committee and Technical Subcommittee for approval, Block list approval, Licensing authority of DGDA, Inspection report for Pharmaceutical industry and retail outlets.
Power Point Projection
Inspection report for Pharmaceutical industry and retail outlets
Directorate General of Drug Administration of Bangladesh has great lack of manpower for the monitoring of drug production in large numbers of Allopathic, Ayurvedic, and Unani medicines manufacturing industries and numerous pharmacies distributed all over the country. According to the information of the Directorate General of Drug Administration (DGDA) of Bangladesh website, DGDA has offices of Drug Superintendent only in 34 districts (out of 64 districts) all over the country. The Drug Administration does not have Drug Superintendent even in every district let alone every Upazila. It is impossible to control the production and marketing of drugs with this less manpower all over the country. As a result, Drug Administration does not have strict controlling power on pharmaceutical industries and retail and wholesale pharmacies. Yet it’s a matter of hope that the present Govt. has taken initiative recently and DGDA is on the process for the recruitment of Drug Supers and Drug Inspectors. According to the available information, the Govt. is not going to appoint Drug Super in any Upazila. Without Drug Super in Upazila level, it would not be possible to control the drugs strictly.
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 66 C. Communication in Pharmaceutical Industry and Regulatory Affairs
Lecture 17. Communication with Regulatory Body (Continues…)
Line Up: International Marketing and Trade Related Barriers: Communication for outsourcing (contract manufacturing), technology transfer, Letter of Credit (LC) opening for export and Import.
International Marketing Communications (Promotion)
Media Choices for International Marketing
Marketing communications in international markets needs to be conducted with care. This lesson will consider some of the key issues that are to take into account when promoting products or services in overseas markets. There will be influences upon media choice, cultural issues to be considered, as well as the media choices themselves - personal selling, advertising, and others.
Influences upon International Media Choice.
There are a number of factors that will impact upon choice and availability of media such as:
The nature and level of competition for channels in target market.
Whether or not there is a rich variety of media in your target market.
The level of economic development in target market (for example, in remote regions of Africa there would be no mains electricity on which to run TVs or radios).
The availability of other local resources to assist promotional campaign will also need to be investigated (for example, sales people or local advertising expertise).
Local laws may not allow specific content or references to be made in adverts (for example, it is not acceptable to show naked legs in adverts displayed in Muslim countries).
And of course a lot depends upon the purpose of the international campaign in the first place.
Cultural Issues and International Marketing Communications.
There are a whole range of cultural issues that international marketers need to consider when communicating with target audiences in different cultures.
Language will always be a challenge. One cannot use a single language for an international campaign. For example, there are between six and twelve main regional variations of the Chinese languages, with the most popular being Mandarin (c 850 Million), followed by Wu
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 67
(c. 90 million), Min (c. 70 million) and Cantonese (c. 70 million). India has 22 languages including Assamese, Bengali, Bodo, Dogri, Gujarati, Hindi, Punjabi, and Tamil to name but a few. Of course language choice could affect branding choices, and the names of products and services.
Design, symbolism and aesthetics sometimes do not transcend international boundaries. For example Japanese aesthetics sometimes focus upon taste and beauty. Also look at Japanese cars from the front - they have a smiling face.
The manner in which people present themselves in terms of dress and appearance changes from culture to culture. For example in Maori culture, dress plays a central role with everyday clothing differing greatly from ceremonial costume. Whereas in Western business- culture the standard 'uniform' tends to be a conservative collar and tie.
Other factors that need to be considered in relation to international marketing
communications (Promotion) include:
The work ethic of employees and customers to be targeted by media.
Levels of literacy and the availability of education for the national population.
The similarity or diversity of beliefs, religion, morality and values in the target nation.
The similarity or diversity of beliefs, religion, morality and values in the target nation.
The family and the roles of those within it are factors to take into account.
Media Choices in International Marketing. Personal Selling in International Marketing.
Personal selling has a number of pros and cons:
It is beneficial where wages tend to be low, since staffing costs will be comparatively low.
Where there are many languages, you'll need trained sales personnel that can convey your message in specific tongues (see culture above).
The sales force will need to be supported. Commercial administration staff will have to take care of sales enquiries, send out product literature and samples, and make quotations - often online.
You'll need to invest time and effort in recruiting, motivating, organizing and training a local sales force. Recruits will need to know about products and markets, language and culture, the location of target segments, customer buyer behavior - and that's just the beginning.
There is a dilemma as to whether to place expatriate employees into your international target market, or to recruit locally. Local is best!
PHARMACEUTICAL COMMUNICATION (PHR 207) WORLD UNIVERISTY OF BANGLADESH Page 68
Where business etiquette varies from culture to culture, you'll need to train your people in what to expect - or recruit salesmen from the local market.
Advertising in International Marketing.
Advertising has a number of pros and cons:
When considering press advertising try to anticipate the levels of literacy within the nation in question. Where literacy levels are lower, perhaps you could use a more visual campaign.
Which language(s) is the press written in?
What is the split between regional and national press in your target market?
What types of television channels are available? Are they HDD, digital, analogue, satellite, cable, via the telephone, via a broadband or ADSL connection?
Which TV channels do our target segments watch?
Is there space on the suitable TV channels when we want it, or at a price that we can afford?
Where visual communication is paramount, are there suitable poster locations?
What is the behavior of the target population in relation to cinema? For example, Cinema is tremendously popular in India.
Radio has similar issues as TV and press. Which stations do your target groups listen to - news, sports or music? Is there space available with the most suitable stations?
Other Media Choices in International Marketing.
Other potential media would include:
Web-based marketing using your own domestic site, or one developed specifically for the target market. Chinese websites are very different to Western sites. They are very busy and every single space is filled with images and text. Affiliate or pay-per-click advertising may be available.
International tradeshows, trade missions, sponsorship (for example international sporting events), Public Relations (for example oil companies) and a variety of other