Introduction to Pharmaceutical Analysis 2 (QC2 2nd year - 2nd sem)

Pharmaceutical Analysis

◈ also known as Analytical Chemistry or Quantitative-Qualitative Chemistry

Pharmaceutical Analysis

◈ branch of chemistry that provides information relative to the composition of matter (chemical composition, structure, behavior)

- Qualitative

- Quantitative

Pharmaceutical Analysis

◈ has two major divisions:

- Qualitative

- Quantitative

2 DIVISIONS of Pharmaceutical Analysis

QUALITATIVE

involves the identification of components in a given sample

QUALITATIVE

it gives the identity of the chemical species present in the sample

QUALITATIVE

Quality or character of chemical

QUALITATIVE

determination composition of chemical

QUALITATIVE

Ascertainment of impurities present in a given sample

QUALITATIVE

Answers the question: "What is present in a given sample?"

QUANTITATIVE

involves the determination of the proportion/number of components in a given sample.

QUANTITATIVE

Answers the question: "How much is present in the sample?"

Why is it important to get the pharmaceutical analysis done?

◈ because everybody needs supplements and medicines. Since these drugs are made with complex compounds that cannot go wrong or divert from the prescribed ingredients, it is very important that these drugs go through thorough checking and testing. This testing is in terms of the chemical compounds, raw materials, and the proportioning of these things.

◈ To carry out the tests, they must follow some prescribed procedures and methods for testing all kinds of impurities. The USP 232 and 233 have all the specified limit tests and procedures. It has been a mandate that all pharma products and other drugs must comply with the standards to test for impurities.

Why is it important to get the pharmaceutical analysis done?

Pharmaceutical Analysis reveals the categorization, identification, and determination of raw materials and final product outcomes.

Different types of drugs are coming into the market almost every day and rising at an alarming rate. What's concerning is that there are either totally new products or just a modification of an existing one.

To ensure that these new batches of drugs are safe for human consumption, it is important to do a pharmaceutical analysis. New analysis methods are also coming up with every new drug coming out!

Importance of Pharmaceutical Analysis

◈ identity of the drug in the formulated product

◈ determination of active ingredient or additional impurities stability of the drug

◈ rate of the drug from its formulation

◈ identity and purity of pure drug that meets specification concentrations of specified impurities

◈ concentrations of drug in plasma or biological fluids

◈ determine pKa values, partition coefficients, and solubilities (physicochemical properties)

◈ stability of drug under development

Pharmaceutical Analysis is NEEDED when;

◈ at times when the present process and procedures need solvents and reagents that are expensive to deal with

◈ if it includes any separating or tedious extraction step that is not just time-consuming but expensive, too

◈ in the case when research institutes need detailed analysis report

◈ if the process is not reliable, sensitive, and fast

◈ when needed by quality control departments

- Sample Size

- Extent of Determination

- Nature of Methods

- Material used

Classification of ANALYSIS based on the following:

1. Ultra

2. Micro

3. Semi micro

4. Macro

Sample Size

Ultra

less than 1mg

Micro

1-10mg

Semi micro

10-100 mg

Macro

100mg -1g

1. Proximate

2. Ultimate

Extent of Determination

Proximate

- total amount of class or group of active plant principles in a given sample.

Proximate

- estimate

Ultimate

- amount of specific compartment/ single species present in the sample.

1. Classical

2. Instrumentation

3. Miscellaneous / Specific method

Nature of Methods

Classical

- a.k.a General / Chemical

Classical

- chemical or stoichometric reactions

Classical

- analyte and titrant

Instrumentation

- based on the physical or chemical properties of the analyte

Instrumentation

- polarimetry or refractometry

Miscellaneous / Specific method

- involves crude drugs and natural products derived from

1. Chemical

2. Physical

3. Biological

Material Used

Chemical

- use of chemical reagents

Physical

- instruments & special apparatus

Biological

- use of microorganisms, animals, marine life

1. Quality Assurance / Quality Control (major application)

2. Medicine: Clinical Assay

3. Monitoring geological sample

4. Pharmceutical Industry

5. Food & Agriculture

Application of Pharmaceutical Analysis

- WHO

- ASEAN

- ICS

- ISO

- PIC/S

Organizations/Agencies involved in ensuring Pharmaceutical Quality

World Health Organization

is a specialized agency of the United Nations responsible for international public health.

WHO Constitution

establishes the agency's governing structure and principles.

WHO

Its main objective is "the attainment by all people of the highest possible level of health."

The development of norms, standards and guidelines to promote quality assurance, medicines regulation and safety of medicines is an integral part of WHO's Constitution and a unique responsibility on which member countries rely on and to help them in implementing it.

International Conference on Harmonisation

ICH

ICH

Committee that provides the pharmaceutical stability guidelines for stability conditions and testing to be followed by industries throughout the world for product quality

ICH

Technical requirements for registration of pharmaceuticals for human use pioneered by the EU in the 1990s to facilitate the move towards a single market for Pharmaceuticals

ICH

This was a Bilateral discussion between Europe, Japan, and the USA at the WHO Conference in 1989 in Paris; an agreement was reached to initiate a joint regulatory- industry initiative for international harmonization thus, ICH was borne in April 1990 (Brussels)

ICH

To improve the efficiency of new drug development and registration processes

ICH

To promote public health, prevent duplication of clinical trials in humans, and minimize the use of animal testing without compromising safety and effectiveness

Q1F

- stability data package for registration application in climatic zones III and IV

Q2 (R1)

- VALIDATION OF ANALYTICAL PROCEDURE: Text and Methodology for analytical method validation for stability studies

Q3A (R2)

- IMPURITIES IN NEW DRUG SUBSTANCE: it has information about ICH guidelines for impurities in active pharmaceutical ingredients

Q3B (R2)

- IMPURITIES IN NEW DRUG PRODUCTS: This part of ICH stability guidelines for stability testing has information of impurities in pharmaceutical finished products

Q3C (R5)

- IMPURITIES: guidelines for determination of residual solvents in substances and drug products.

Q4

- Pharmacopoeia

Q4A

- Pharmacopoeia Harmonization - Details about the harmonization of pharmacopeias like USP, JP, and EP

Q4B

- guidelines for evaluation and recommendation of pharmacopoeial Texts for Use in the ICH regions

Q4B Annex 12

- Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Analytical Sieving

Q4B Annex 13

- Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Bulk Density and Tapped Density of Powders

Q4B Annex 14

- Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Bacterial Endotoxins Test

Q4B

- Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions

Q5A(R1)

- Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

Q5B

- Quality of Biotechnological Products: Analysis of the Expression Construct in Cells used for the Production of I-DNA Derived Protein Products

Q5C

- Quality of Biotechnological Products: Guidelines for stability testing of Biotechnological/ Biological Products

Q5D

- Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/ Biological Products

Q5E

- Comparability of Biotechnological/ Biological Products Subject to Changes in their Manufacturing Process

Q6A

- Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances

Q6B

- Specifications: Test Procedures and Acceptance Citeria for Biotechnological/ Biological Products

Q7

- ICH Q7 guidelines have Good Manufacturing Practice Guide for APis (Active Pharmaceutical Ingredients) during the manufacturing process

Q8(2)

- Pharmaceutical Development

Q9

- Quality Risk Management: Recommendations for evaluation of Risk involved in manufacturing processes.

Q10

- Pharmaceutical Quality system: Recommendations o maintain the quat of the product.

Q11

- Development and Manufacture of Drug Substances (Chemical Entries and Biotechnological Biological Entities

Q12

-Lifecycle Management: Guidelines on lifecycle management of pharmaceutical products.

Q13

- Continuous Manufacturing of Drug Substances and Drug Products: Provide guidance to industry and. regulatory agencies regarding regulatory expectations on the development implementation, and assessment of CM technologies used in the manufacture of drug substances and drug products.

Q14

- Analytical Procedure Development

ISO

Is the world's largest developer of voluntary International Standards. These standards give state-of-the-art specifications for products, services, and good practice, helping to make the industry more efficient and effective

ISO

Top management shall provide evidence of its commitment to the development and implementation of the Quality Management System and continually improve its effectiveness (ISO 9000-2008)

ISO

Developed through global consensus, they help to break down barriers to an international trader

- Geneva, Switzerland

- 178

ISO's Central Secretariat is in ________, with _____ ISO members

ISO

Provides requirements, specifications, guidelines, or characteristics that can be used consistently to ensure that materials, products, processes, and services are fit for their purpose

ISO

Ensure that products and services are safe, reliable, and good quality.

o minimizing waste and errors

o increase productivity

o help access new market

o levels the playing field for developing countries

- In businesses and companies, ISO standards can reduce costs by:

ISO

Has several management system standards, each focusing on different issues affecting global business

- Quality Management

- Environmental Management

- Food Safety Management

- Energy Management

ISO Management System Standards, examples;

Quality Management

ISO 9000 family

Environmental Management

ISO 14000 family

Food Safety Management

ISO 22000 family

Energy Management

ISO 50001 family

PIC (Pharmaceutical Inspection Convention)

was founded in October 1970 by EFTA (European Free Trade Association) under the title "The Convention for the Mutual Recognition of Inspections in Respect of the Manufacture of Pharmaceutical Products."

The Convention for the Mutual Recognition of Inspections in Respect of the Manufacture of Pharmaceutical Products.

PIC (Pharmaceutical Inspection Convention) was founded in October 1970 by EFTA (European Free Trade Association) under the title "_____________________"

- October 1970

- EFTA (European Free Trade Association)

PIC (Pharmaceutical Inspection Convention) was founded in _______ by ________ under the title "The Convention for the Mutual Recognition of Inspections in Respect of the Manufacture of Pharmaceutical Products."

PIC Scheme (Cooperation)

was formed on Nov 2, 1995.

PIC/S

PIC and the PIC Scheme, which operate together in parallel, are jointly

referred to as ______. USA has been a member since 2011

PIC/S

Mission is "to lead the international development, implementation, and maintenance of harmonized Good Manufacturing Practice (GMP) standards and quality systems of inspectorates in medicinal products".

PIC/S

provides active and constructive cooperation in the field of GMP(Good Manufacturing Practice).

purpose of PIC/S

"to facilitate the networking between participating authorities and the maintenance of mutual confidence, the exchange of information and experience in the field of GMP and related areas, and the mutual training of GMP inspectors."

"Association of Southeast Asian Nations"

ASEAN

ASEAN

is a regional intergovernmental organization comprising ten Southeast Asian countries, which promotes intergovernmental cooperation and facilitates economic, political, and security cooperation among its ten members

ASEAN

Founded: 8 August 1967, Singapore