Excipient Manufacturing, Characterization, and Quality Control

EXCIPIENTESSENTIALS

Excipient Manufacturing, Characterization, and Regulatory Process Development

Introduction to ExcipientsThe pharmaceutical industry has rigorous regulatory guidelines and rules to follow during active pharmaceutical ingredient (API) testing. For excipients, the most frequently used guideline is from the International Pharmaceutical Excipient Council (IPEC).

More recently, the ICH Q3A (2) Guidance (Impurities in New Drug Substances) was issued to provide “guidance for registration applications on the content and qualification of impurities in new drug substances.” Note that ICH Q3A applies to drug substances and ICH Q3B applies to drug products, but neither applies to excipients.

Excipient manufacturing and process development for its use in drug production must meet good manufacturing practices (GMP) compliance. The suitability of pharmaceutical excipients for their intended use is defined by critical quality attributes (CQAs) such as identity, strength, and purity, which can pose numerous analytical challenges due to the complex nature of excipients.

Classes of substancesused as excipients

SEMI-SYNTHETIC SUBSTANCES

NATURAL SUBSTANCES

SYNTHETIC SUBSTANCES

EXCIPIENTS

ORGANIC INORGANICSIMPLE /COMPLEX

SYNTHETICSEMI-

SYNTHETIC

NATURAL

Excipient Manufacturing, Characterization, and Regulatory Process Development

Pharmaceutical Excipients – The United States Pharmacopeia (USP) ViewUnderstand the regulatory framework for excipients testing, with a viewpoint on the USP Stimuli article, titled, The Complexity of Setting Compendial Specifications for Excipient Composition and Impurities which provides continued guidance on how to specify excipient composition, including control of impurities.

Article: Understanding Excipient Testing Regulations

Nominal

Substance typically found in the excipient that is expressed by the official name and definition and/or assay provided in the USP monograph.

Simple

An excipient composed of a single main substance with a well-defined chemical structure that can be well characterized analytically.

Concomitant

A minor component of an excipient that accompanies the nominal component that is identified either in the title or definition of a monograph. Concomitant components are characteristic of many excipients and are not considered to be impurities if there is no negative impact on drug products.

Complex

Any excipient that does not fit the definition of a simple excipient.

Minor component

A component of an excipient that is not the nominal component or, where the official name does not relate to the excipient components, not the major component.

Impurity

Any substance that detracts from the quality of the excipient (i.e., that is not the substance appearing in the official name, or a concomitant component or added substance).

Excipient Manufacturing, Characterization, and Regulatory Process Development

Thinking Beyond APIs: Understanding the Role of Excipients in MedicinesWhether it’s ibuprofen for a headache or statins for heart conditions, the public assumes the medicines they are taking are safe and effective. Most medicines contain both active and non-active substances. The active substances are most often delivered with an excipient, a substance used alongside the active ones for long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts, facilitating drug absorption, reducing viscosity, or enhancing solubility.

The lack of regulatory controls around excipients, including defining any impurity thresholds, pose a significant risk. To ensure the purity, quality, and safety of any drug substance, it is essential to perform rigorous analytical tests and have a thorough quality assurance plan in place.

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ARTICLE

Simplifying the Evaluation of Pharmaceutical ExcipientsThis on-demand webinar, Strategies to Simplify the Evaluation of Pharmaceutical Excipients, is led by industry experts Dr. Moritz Perscheid, Head of Pharma Services at LGC, and Kieran Evans, Applications Scientist at PerkinElmer.

They discuss the numerous challenges associated with detecting impurities in excipients and propose potential strategies for simplifying the process.

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WEBINAR

Excipient Manufacturing, Characterization, and Regulatory Process Development

Common Excipient Analysis: LactoseWant to know more? Explore our application notes.

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A High-Sensitivity, High-Speed DSC Technique:

Measurement of Amorphous Lactose

The Application of Mesh Material Pockets in DMA Analysis of Amorphous and Crystalline Lactose

Powders

Quantitation of Amorphicity of Lactose Using Material Pockets

Our technology solutions featured in these applications:

APPLICATION NOTES

Excipient Manufacturing, Characterization, and Regulatory Process Development

Common Excipient Analysis: Raw Material IdentificationWant to know more? Explore our application notes.

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APPLICATION NOTES

Analysis of Pharmaceutical Raw

Materials Through Packaging Using an

FT-NIR Fiber Optic Probe

Analysis of Pharmaceutical Raw Materials Using the

Tri-Range Spectrum 3 Infrared Spectrometer

Verification of Pharmaceutical Raw Materials Using the

Spectrum Two N FT-NIR Spectrometer

A Comparison of Two FT-NIR Sampling Techniques for SIMCA Classification of

Spectroscopically Similar Pharmaceutical Raw Materials

Our technology solutions featured in these applications:

Excipient Manufacturing, Characterization, and Regulatory Process Development

Common Excipient Analysis: Excipient ImpurityWant to know more? Explore our application notes.

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APPLICATION NOTES

Detection and Quantification of Formaldehyde by Derivatization with Pentafluorobenzylhydroxyl Amine in Pharmaceutical Excipients by Static

Headspace GC/MS

Testing and Validation of Various Antacids for Elemental

Impurities using the NexION 2000 ICP-MS

Our technology solutions featured in these applications:

Excipient Manufacturing, Characterization, and Regulatory Process Development

Common Excipient Analysis: Content UniformityWant to know more? Explore our application notes.

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APPLICATION NOTES

Whole Tablet Measurements Using

the PerkinElmer Tablet Analyzer

Creating Custom Tablet Holders for the Tablet

Autosampler

Tablet Analyzer with Near-Infrared

Autosampler

Our technology solutions featured in these applications:

Excipient Manufacturing, Characterization, and Regulatory Process Development

Common Excipient Analysis: Moisture and Loss on DryingWant to know more? Explore our application notes.

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APPLICATION NOTES

Better Characterizations Start with Better Control

Moisture can influence the physical and chemical properties of excipients, so it is essential to verify moisture during the manufacturing process of raw materials and finished products.

TGA instruments are a popular method used in monographs to regulate loss on drying for both API and excipients.

Learn more how our best in class TGA can support your loss on drying testing.

Our technology solutions featured in these applications:

Excipient Manufacturing, Characterization, and Regulatory Process Development

Excipients CharacterizationMaximize Drug Product Quality by Using High Quality Excipients

When you control every step of the excipient manufacturing process, you’re ensuring the excipient consistently meets required good manufacturing practices (GMP) compliance. The suitability of an excipient is defined by its composition, strength, and purity—all of which can be identified and achieved with our instruments, consumables, and services.

Excipient Manufacturing, Characterization, and Regulatory Process Development

Analytical Techniques and Applications in Excipient AnalysisIdentify and characterize your excipients while ensuring 21 CFR Part 11 compliance from sample preparation to obtaining accurate results by taking advantage of our complete array of solutions for unparalleled performance, accuracy, and confidence.

MOLECULAR SPECTROSCOPY THERMAL ANALYSIS CHROMATOGRAPHY ATOMIC SPECTROSCOPY

Infrared Spectroscopy (FT-IR)

n Simple raw material identification

n Differentiation between grades of materials (NIR)

n Excipient distribution analysis (IR Microscopy)

Differential Scanning Calorimetry (DSC)

n Determination of amorphous content

n Excipient-excipient interactions

n Drug-excipient interactions

Thermogravimetric Analysis (TGA)

n Moisture content

n Degradation analysis

n Evolved gas analysis when combined with other techniques (such as IR)

Atomic Spectroscopy (ICP-MS, ICP-OES and AA)

n Elemental impurities

n Trace elements analysis

Chromatography (LC systems)

n Moisture content

n Degradation analysis

n Evolved gas analysis when combined with other techniques (such as IR and GC/MS)

Excipient Manufacturing, Characterization, and Regulatory Process Development

Infrared Microscopy – A Technique for Determination of Excipient Distributionn IR microscopy allows materials to be analyzed at a microscale.

n Infrared images may be used to visualize material distribution in a final product.

n Samples are first cut to expose a flat surface and a visible image is acquired.

Visible image of a tablet showing area selected for infrared imaging. Material: Lactose Correlation: 0.98 Area: (%)

Infrared image demonstrating distribution of lactose based on correlation with a reference lactose spectrum.

Excipient Manufacturing, Characterization, and Regulatory Process Development

Never Miss a Peak in Your QC Lab

Browse Consumables by Technology—Trust the Consumables Engineered for Your Instruments

Whatever your separation challenge, your choice of liquid chromatography (LC) column can make all the difference.

We only select the highest quality products for our consumables portfolio and invest heavily to test and validate the quality of our products which provide reliable performance, control operating costs, and maximize the uptime of your instrument.

Excipient Manufacturing, Characterization, and Regulatory Process Development

The Best Answers Happen When Great Technologies Connect

TG-IRn Residual solvent

n Moisture analysis

n Formulation analysis

TG-MSn Residual solvent

n Solvates

n Crystal shape evaluation

n Solvent-molecule binding energy

TG-GC/MSn Residual solvent

n Solvates

n Crystal shape evaluation

n Excipients compatibility

n Shelf life

n Thermal degradation

TG-IR-GC/MSn Residual solvent

n Formulation analysis

n Solid state characterization (polymorphism/pseudopolymorphism)

n Solvates

n Crystal shape evaluation

n Excipients compatibility

n Shelf life

n Thermal degradation

Excipient Manufacturing, Characterization, and Regulatory Process Development

USP <1058> Analytical Instrument QualificationThis informational chapter provides general guidance in a scientific, risk-based approach for carrying out an analytical instrument qualification (AIQ). This chapter uses various terms, acronyms, and activities common to analytical laboratories and validation disciplines.

PerkinElmer offers several traditional qualification protocols and services for lab instruments, ensuring complete, consistent, and accurate data. Our services provide:

n Qualification protocols using calibration standards

n Custom protocol development

n Execution of customer-developed protocols

n IQ/OQ protocol library to leverage

Analytical Instrument Qualification

Analytical Method Validation

System Suitability Tests

Quality Control Check Samples

COMPONENTS OF DATA QUALITY:

Many analysts carry out their tests on instruments that have been standardized by using reference materials and/or calibration standards. Some analyses also

require the inclusion of quality control check samples to provide an in-process or ongoing assurance of the test's suitable performance.

System suitability tests verify that the system will perform in accordance with the criteria set forth in the procedure.

Analytical method validation is the collection of documented evidence that an analytical procedure is suitable for its intended use.

AIQ is the collection of documented evidence that an instrument performs suitably for its intended purpose.

Use of a qualified instrument in analyses contributes to confidence in the validity of generated data.

Excipient Manufacturing, Characterization, and Regulatory Process Development

Laboratory Services

Integrity at the heart of your lab.

Advance cohesiveness and confidence knowing that your labs are operating within

global regulatory requirements.

Project and program based computerized system validation (CSV) support to meet your needs and ensure that instrument data is complete,

consistent and accurate.

Instrument qualification approaches customized for your lab; from traditional to electronic.

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