outsourcing How to help your CMO meet your lead time P.J. Noyes

As appeared in
Tablets & Capsules April 2012, Copyright CSC Publishing
How to help your CMO meet your lead time
David Simpson
P.J. Noyes
This article addresses factors and challenges associated with
determining a new product’s lead time and how you can help
your CMO keep the project on track.
lmost every manufacturing project starts with the
question, “What’s your lead time?” I can hear the snickers
already. It has almost become a joke when the answer is,
“Four to 6 weeks.” Frustratingly, the lead time often
becomes 10 to 12 weeks, or more. When it is vital for
your business to have a product delivered on time, and
being on time requires relying on your CMO, it helps to
know some of the factors that determine a realistic lead
time and keep your project on schedule.
Regulatory categories
It is important to determine the regulatory category of
your products from the outset. Those involved in the Rx,
OTC, or dietary-supplement industries can appreciate
how regulatory requirements can affect a timeline. To
start the project on a good note, ask yourself:
• Does the product and/or active ingredient(s) meet a
specific monograph?
• Is it a new dietary ingredient (NDI)?
• Is USP testing desired or required?
• Has stability testing been started to support label
claims and expiration dating?
The answers to these questions can help you determine a realistic timeline. Working with sound legal counsel to understand and navigate structure-function label
claims and monographs is also recommended.
Specifications for raw materials, components, and
finished product
Unless clearly defined from the start and communicated throughout the project, specifications can derail a
lead time in a blink. Determine whether you will supply
the raw materials and components or if you are looking
for a turnkey solution. Often a CMO has a broader network of suppliers and better purchasing power, so it may
be able to help manage your costs. Keep in mind that
minimum-purchase requirements may lead to excess
materials being stored. It is also not uncommon to have
stored items priced as a separate line item above and
beyond the unit cost of the product.
Also consider what specifications the material and
components must meet. Questions you should be able to
answer include:
• What type of package is required (HDPE, PET,
pouch/film, glass, etc)?
• For specified extracts, what part of the plant is used?
Has alcohol been used in your product? If so, what is
it denatured with? For active pharmaceutical ingredients (APIs) or vitamins, what strength is required (4to-1, versus 400-to-1)?
• Is an international source acceptable or is a domestic
source required?
• Have you defined the type of label (paper, laminate,
or shrink) and the label coating required? How
about the type of adhesive and the wind direction
for adhesive labels?
• What is the density of your capsule ingredient(s)?
Have you confirmed that your dosage will fit inside
the capsule you specified?
• Have shipping trials been completed to determine
the type of cardboard to use? How does your preferred packaging hold up to temperature changes
during transport and storage? Is there a friability
issue with your tablets because there is no cotton
used in the bottle? Are your labels getting scraped
and scuffed because of the laminate used or because
the dividers are too tight?
Supply chain
Supply chain issues challenge even the best CMO and
branded-goods company. Lead times on components and
raw materials are affected by many factors, including
location, availability, transportation, production schedules for a specific component, and even the weather.
Delays may arise if materials have to go through customs
or aren’t available. In some cases, the wrong material or
component is shipped, and by the time it comes in,
you’ve already lost several weeks.
The biggest challenge is maintaining control over a
variety of vendors. Having a backup supplier can save
considerable time and help manage costs. For example,
recent shortages of turmeric or jojoba oil may have added
weeks to a production schedule. It is also important to
keep in mind that CMOs and brand owners also face
daily challenges, ranging from equipment breakdowns to
scheduling conflicts. Accounting for supply chain issues
and defining what the longest lead time is for a material
will help establish a production start date.
Testing comes with many differing opinions and practices. As the FDA continues its review of brand owners’
claims—and determines whether manufacturers are in
compliance with cGMP guidelines such as 21 CFR 210,
211, and 111 specific to OTCs and dietary supplements
—the importance of understanding testing’s role in establishing a production timeline is essential for avoiding
delays. Recent reviews of FDA warning letters and 483s
show that the following tests are often absent:
• Incoming raw material testing,
• Package stability/integrity, and
• Finished-good testing, including stability, microbial,
and assay(s) of actives.
Also consider if an in-house lab or qualified thirdparty lab will be used for the tests. If your CMO is partnered with an outside lab, the lab is likely providing services to multiple accounts and may not always be able to
rush a project. Also, make sure your CMO has audited
and validated its lab partners.
We’ve all heard the phrase, “If it isn’t written down, it
didn’t happen.” In the manufacturing industry, we can
pretty much guarantee there will always be a need for a
paper trail. The following are documents that you can
expect to include and that can require extensive time to
Certificate of analysis. A certificate of analysis (CoA)
is supplied by the raw material supplier and details the
makeup of the material. This document is used to ensure
that the material received is the correct material for use in
the formula. Remember that until a supplier and three lots
of its material have been qualified, as well as one lot annually thereafter, quality inspection and receiving personnel
cannot rely solely on the CoA to release a raw material.
Certificate of compliance. The certificate of compliance (CoC) is a CoA, but for components. The document lists specific characteristics such as color, resin or
glass information, type of adhesive used on labels, dimensions, and other criteria.
Finished-good specification sheets. A document usually supplied by brand owners. It provides details on how
the finished product should look, be packaged, and be
configured on the pallet.
Inspection sheets. A quality document drafted by your
CMO for inspecting all components and raw materials.
Material safety data sheet. The material safety data
sheet (MSDS) informs workers and emergency personnel
about procedures for handling or working with that substance in a safe manner and lists information about physical data, toxicity, health effects, first aid, reactivity, storage, disposal, protective equipment, and spills.
Supply agreements. This document defines the partnership between you and your CMO and the responsibilities between the brand owner and the CMO. Remember
that if you’d like to have legal consultation, it can add
considerable time.
Quality agreements. This document sets the parameters for the quality of the product. It details who will be
responsible for the testing, retained product, label claims,
recalls, customer complaints, and other details.
Certificate of insurance. If you’re launching a new
product, a certificate of insurance (COI) may not be
something you’ve thought to share with a CMO.
However, in most cases, both parties will exchange a
COI that provides insurance coverage for both parties.
Amounts vary from company to company and depend on
the product.
Stability protocol. This report details the types of
testing to be performed, what methods will be used, and
how many samples would be needed prior to starting a
stability study.
Master formula or batch records. Master formula
records (MFR) or master batch records (MBR) are often
missing during FDA inspections. These records are essential to ensure that a product is made in a consistent manner.
Process validation. Required for OTC products and
strongly recommended for dietary supplements, process
validation uses the MBR. It requires the same process be followed in three consecutive batches to validate process uniformity and consistency in batching and packaging of a
Lab, pilot, and production batches
Do you have a finished formula and process or one that
just requires a little tweaking? The answer could mean the
difference of several weeks or several months. Once you do
get a production batch, often the finished-good testing has
not been factored in. But it is necessary to make sure that
the product is safe, effective, and meets label claims. As the
popular saying goes, “You can’t hurry bugs.” Plan for at least
5 days of microbial testing, as well as assays, if there are
actives listed in the drug fact or supplement panel.
Equipment requirements are often a factor as well,
even for existing products. It’s often thought that a “filler
is a filler, a tank a tank”, but spend a few minutes talking
with manufacturers, and you’ll find that moving a formula
and process from one CMO to another may seem easy,
but has many variables. Check with your CMO to see if
its process includes a lab batch and/or a scale-up pilot
batch before moving into production. If not, make sure
you’ve specified in the supply agreement which company
is responsible for a failed batch.
This article addresses a few of the factors that affect
lead time. Remember that clear, constant communication
with your CMO is key. Also, defining your timeline from
the beginning and working with your account manager or
project manager can help you determine whether it’s realistic. Don’t be afraid to share your thoughts and experiences from a brand owner’s perspective. Let us know how
we in manufacturing can work with you to meet your lead
David Simpson is business development manager at P.J. Noyes, 89
Bridge St., Lancaster, NH 03584. Tel. 800 522 2469, fax 603
788 3873. Website: www.pjnoyes.com. P.J. Noyes is an FDAregistered, GMP-compliant, and NSF Certified-for-Sport contract
manufacturer and packager for the nutraceutical and pharmaceutical industries. It is committed to working with companies of all sizes,
from R&D projects to production, in tablets, capsules, and liquids.